Ki-67

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Ki-67

  • marker ki-67
  • proliferation marker ki-67

  • Terms modified by Ki-67

  • ki-67 antigen
  • ki-67 expression
  • ki-67 immunostaining
  • ki-67 index
  • ki-67 labeling index
  • ki-67 labelling index
  • ki-67 li
  • ki-67 pi
  • ki-67 proliferation index
  • ki-67 staining

  • Selected Abstracts


    Role of canine basal cells in postnatal prostatic development, induction of hyperplasia, and sex hormone-stimulated growth; and the ductal origin of carcinoma,

    THE PROSTATE, Issue 3 2001
    Irwin Leav
    Abstract Background The canine prostate has often been proposed as a model for abnormal growth of the human gland. Hyperplasia of the prostate is common in aging men and has been estimated to be present in 100% of old intact dogs. While prostatic carcinoma is common in older men, it appears to be rare in dogs and unlike the disease in humans, it occurs with relatively high frequency in castrated animals. Since basal cells are thought to be key participants in normal and abnormal growth of the human gland, we used immunohistochemistry to investigate the role that they may play in canine prostatic development, the evolution of hyperplasia and carcinoma, and the effects of sex hormones on these cells. Methods Prostate specimens were obtained at autopsy from seven sexually immature dogs, autopsy and biopsy samples from 14 sexually mature intact animals, from four castrates, and from19 dogs with prostatic carcinoma. In addition, we also studied the prostates from two intact dogs treated with 5,-dihydrotestosterone (DHT) for 6 months and two castrated dogs that were subsequently treated with 5,-androstane-3, diol and estradiol-17,, as well as specimens from two sexually ablated animals given DHT for 2 weeks. All specimens were immunostained for high molecular weight cytokeratin (HMC), pancytokeratin, androgen receptor (AR), and the proliferative marker KI-67. Results We find that basal cells are the major proliferative cell type in the neonatal and adult canine prostate and that the expression of HMC staining, which defines these cells, may be regulated by androgens. In the adult gland, ductal basal cells formed a contiguous layer, whereas those lining acini were discontinuous. Populations of both basal cell types were variably AR positive, but while HMC immunostaining was abolished in acinar cells following long-term castration, staining remained in ductal cell counterparts. Paralleling the histological development of hyperplasia, the acinar basal cell population increased with age and were the major cell type that expressed KI -67. In contrast, ductal basal cell populations did not expand in the prostates of older dogs and were seldom positively stained for KI -67. The numbers of HMC and KI-67-stained acinar basal cells were dramatically increased in the prostates of intact dogs treated with DHT when compared with glands of untreated controls. This was not the case with ductal basal cells. Androgens given alone or together with estrogen to castrated dogs induced widespread HMC and KI -67 immunostaining in both populations of basal cells. In addition, our results indicate that the majority of canine prostatic carcinomas likely arise exclusively from ductal epithelium. Only one of the 19 cases of carcinoma contained cells that expressed AR, which suggests that androgens may not be required for the initiation or progression of these cancers. Conclusions Our findings indicate that two biologically distinct populations of basal cells may exist in the canine prostate. In this regard, the age-related expansion of proliferating acinar basal cell populations, probably mediated by sex steroids, is a key factor in the pathogenesis of canine prostatic hyperplasia. Additionally, we find that prostatic carcinoma in the dog likely arises from ductal cells. Taken together, these findings may indicate that canine acinar basal cells and ductal epithelium have separate susceptibilities to factors that promote hyperplastic or neoplastic development. Prostate 48:210,224, 2001. © 2001 Wiley-Liss, Inc. [source]


    Analysis of proliferating cell fraction determined by monoclonal antibody to M1-subunit ribonucleotide reductase and Ki-67 in relation to p53 protein expression in fine-needle aspirates from non-Hodgkin's lymphomas

    CYTOPATHOLOGY, Issue 5 2000
    V. Sviatoha
    Analysis of proliferating cell fraction determined by monoclonal antibody to M1-subunit ribonucleotide reductase and Ki-67 in relation to p53 protein expression in fine-needle aspirates from non Hodgkin's lymphomas The purpose of this study was to analyse the proliferative fraction with the monoclonal antibody M1-R-R to M1-subunit ribonucleotide reductase and with MIB-1 to Ki-67 antigen in relation to p53 protein expression in fine needle aspirates from B-cell non-Hodgkin's lymphomas. One hundred and thirty-seven cases, previously diagnosed and sub-typed according to the Kiel classification and characterized by immunophenotyping, were included in the study. The M-1 subunit ribonucleotide reductase (M1 -R-R), Ki-67 and p53 antigens were detected using monoclonal antibodies on stored cytospin preparations. There was a good correlation (r = 0.72) between Ki-67 and M1 -R-R positive cell fraction in both high and low grade lymphomas. High-grade lymphomas had a median percentage of M1 -R-R/MIB-1 positive cells of 53.0/73.0 for lymphoblastic, 61.0/52.0 for immunoblastic and 33.5/41.0 for centroblastic lymphomas, respectively. In low grade lymphomas figures of median percentage of M1 -R-R/MIB-1 were 9.0/15.0 for centroblastic/centrocytic, 11.0/9.5 for chronic lymphocytic leukaemia, 16.0/27.0 for centrocytic and 12.0/9.0 for immunocytomas, respectively. The median percentages of M1 -R-R/MIB-1 for high and low grade lymphomas were 37.0/50.5 and 11.0/12.0, respectively. In the p53 positive cases the proliferation rate as measured by staining for M1 -R-R and MIB-1 was higher than in p53 negative cases, but the difference was not statistically significant. The results show that cytospin material obtained by fine needle aspiration and stored at ,70 °C for years can be used reliably for both peroxidase-avidin-biotin and three-step alkaline phosphatase immunocytochemical staining. In addition, proliferation fraction determined by M1 -R-R monoclonal antibody staining correlates well with that measured by an established marker for cell proliferation, the Ki-67 antibody. However, the proliferation fraction as measured by the two antibodies differs in the various subtypes of non-Hodgkin's lymphoma which indicates that they may contribute different prognostic information. [source]


    Synchronous high-grade squamous intraepithelial lesion and adenocarcinoma in situ of cervix in a young woman presenting with hyperchromatic crowded groups in the cervical cytology specimen: Report of a case

    DIAGNOSTIC CYTOPATHOLOGY, Issue 11 2008
    Nadeem Zafar M.D.
    Abstract We report a 29-year-old woman who underwent routine gynecologic evaluation at a community clinic and had a cervical sample drawn for liquid-based cytologic evaluation. At cytology, many hyperchromatic crowded groups (HCG) were present, but a consensus could not be established whether the abnormal cells were primarily glandular or squamous with secondary endocervical glandular involvement. An interpretation of atypical endocervical cells, favor neoplastic, was rendered and biopsy advised if clinically appropriate. At biopsy, the cervix contained synchronous squamous cell carcinoma in situ, secondarily involving endocervical glands, and neighboring adenocarcinoma in situ. Immunohistochemistry for Ki-67 and p16INK4A crisply and precisely stained both the lesions, clearly separating them from the adjacent uninvolved mucosa. This case re-emphasizes the challenge associated with accurate evaluation of HCG at cytology, the significance of ancillary testing for surrogate markers of high-risk HPV (HR-HPV) infection, the need for adjunct testing for HPV-DNA in the setting of HCG at cervical cytology, and a recommendation to set up studies to evaluate the role of surrogate markers of HR-HPV infection in cytologic samples with HCG. Diagn. Cytopathol. 2008;36:823,826. © 2008 Wiley-Liss, Inc. [source]


    Cytologic comparison of a primary parathyroid cancer and its metastatic lesions: A case report

    DIAGNOSTIC CYTOPATHOLOGY, Issue 1 2006
    I.A.C., Katsuhide Ikeda C.T.
    Abstract We describe the fine-needle aspiration cytology features of a primary parathyroid cancer and of the local recurrent and distant metastatic lesions. The presence of prognostic factors Ki-67 and proliferating cell nuclear antigen (PCNA) was compared immunohistochemically between primary parathyroid carcinoma and related metastatic and recurrent foci. Flow cytometric DNA analysis was also performed to investigate any chromosomal abnormality of the parathyroid carcinoma. Cytologic examination of the endocrine tumor showed that it comprised a loose cohesive cluster and tumor cells with granular cytoplasm and mild nuclear atypia, but for purposes of cytodiagnosis, it is difficult to determine whether such a neoplasm is malignant on the basis of morphology alone. Immunohistochemical analysis showed that Ki-67 and PCNA labeling indices were higher in the recurrent and metastasized carcinomas than in the primary cancer, suggesting that neoplastic cells become more malignant in the recurrent and metastasized foci. To our knowledge, this is the first report describing not only cytopathologic but also immunocytologic differences between primary parathyroid cancer and the metastatic lesion. Diagn. Cytopathol. 2006;34:50-55. © 2005 Wiley-Liss, Inc. [source]


    Aberrant expression of cell-cycle regulator cyclin D1 in breast cancer is related to chromosomal genomic instability

    GENES, CHROMOSOMES AND CANCER, Issue 3 2002
    Jia-Chyi Lung
    To account for the accumulation of genomic alterations required for tumor progression, it has been suggested that the genomes of cancer cells are unstable and that this instability results from defective mutators (the "mutator phenotype" theory). To examine the hypothesis that abnormal cell-cycle regulators act as the mutators contributing to genomic instability, the present study, based on primary tumor tissues from 71 patients with breast cancer, was performed to determine whether there was an association between aberrant expression of cell-cycle regulators (cyclin A, cyclin D1, cyclin E, RB1, p21, and p27) and chromosomal instability. Comparative genomic hybridization was used to measure chromosomal changes, reflecting genomic instability in individual tumors, whereas immunohistochemistry was used to detect aberrant expression of cell-cycle regulators. Overexpression of cyclin D1 was found to be significantly correlated with increased chromosomal instability (defined as harboring more than 7 chromosomal changes), with 63% of tumors overexpressing and 27% of tumors not overexpressing, with cyclin D1 showing chromosomal instability (P < 0.05). Interestingly, this relationship was independent of cell outgrowth (as detected by the proliferation marker Ki-67) and was particularly significant in tumors not expressing p27 or in tumors with detectable RB1. These results suggest that cyclin D1 plays an alternative role in the regulation of genomic stability. © 2002 Wiley-Liss, Inc. [source]


    Disruption of the hyaluronan-based extracellular matrix in spinal cord promotes astrocyte proliferation

    GLIA, Issue 1 2005
    Jaime Struve
    Abstract Astrocyte proliferation is tightly controlled during development and in the adult nervous system. In the present study, we find that a high-molecular-weight (MW) form of the glycosaminoglycan hyaluronan (HA) is found in rat spinal cord tissue and becomes degraded soon after traumatic spinal cord injury. Newly synthesized HA accumulates in injured spinal cord as gliosis proceeds, such that high-MW HA becomes overabundant in the extracellular matrix surrounding glial scars after 1 month. Injection of hyaluronidase, which degrades HA, into normal spinal cord tissue results in increased numbers of glial fibrillary acidic protein (GFAP)-positive cells that also express the nuclear proliferation marker Ki-67, suggesting that HA degradation promotes astrocyte proliferation. In agreement with this observation, adding high- but not low-MW HA to proliferating astrocytes in vitro inhibits cell growth, while treating confluent, quiescent astrocyte cultures with hyaluronidase induces astrocyte proliferation. Collectively, these data indicate that high-MW HA maintains astrocytes in a state of quiescence, and that degradation of HA following CNS injury relieves growth inhibition, resulting in increased astrocyte proliferation. © 2005 Wiley-Liss, Inc. [source]


    Laminin-5 stimulates hepatocellular carcinoma growth through a different function of ,6,4 and ,3,1 integrins,

    HEPATOLOGY, Issue 6 2007
    Carlo Bergamini
    Hepatocellular carcinoma (HCC) growth severely affects prognosis. Ki-67, a known marker of cell proliferation, is a negative prognostic factor in HCC. Growth factors such as the epidermal growth factor (EGF) induce HCC cell proliferation but do not explain the great heterogeneity of HCC growth. Laminin-5 (Ln-5) is an extracellular matrix protein (ECM) present in the tissue microenvironment of HCC. The two main receptors for Ln-5, integrins ,3,1 and ,6,4, are expressed on the cell surface of HCC cells. The aim of this study is to investigate an alternative mechanism of HCC growth whereby Ln-5 promotes HCC cell proliferation through ,3,1 and ,6,4. HCC tissues containing Ln-5 display a larger diameter and higher number of positive cells for Ki-67, a well known proliferative index, as determined by double immunofluorescence staining and real-time PCR on microdissected tissues. In vitro, Ln-5, but not collagen I, collagen IV or fibronectin, induces proliferation as much as EGF does, via Erk phosphorylation as a consequence of ,4 integrin phosphorylation. However, the two HCC cell lines do not proliferate in presence of Ln-5 despite ,4 integrin and Erk1/2 activation. After transfection with ,3 integrin, in the presence of Ln-5 one of these HCC cell lines acquires a proliferative activity whereas one of the proliferative HCC cell lines, knocked-down for ,3 integrin, loses its proliferative activity. Conclusions: Our study suggests a new mechanism of HCC growth whereby Ln-5 stimulates proliferation via a different function of ,6,4 and ,3,1. (HEPATOLOGY 2007.) [source]


    Hepatocarcinogenesis in Female Mice With Mosaic Expression of Connexin32

    HEPATOLOGY, Issue 3 2000
    Oliver Moennikes
    Mice deficient for connexin32 (Cx32), the major gap junction forming protein in liver, are highly susceptible to hepatocarcinogenesis. Because the Cx32 gene is located on the X-chromosome, heterozygous females show mosaicism with respect to Cx32 expression; this enables their use in studying the effect of Cx32-deficiency in a mixed Cx32-plus/Cx32-minus environment in vivo. Female C3H/He mice (Cx32+/+) were crossed with Cx32-deficient C57BL/129Sv males (Cx32Y/- ) to yield F1 females heterozygous with respect to Cx32 (Cx32+/,). Patches of hepatocytes were observed in normal liver that either expressed Cx32 or failed to express the protein. The mean fraction of Cx32-negative tissue in liver was about 60% and did not change significantly with age of mice. Neoplastic liver lesions, induced in weanling mice, were identified in serial liver sections by their deficiency in glucose-6-phosphatase staining. Parallel sections were used for immunohistochemical demonstration of Cx32 protein. Smaller lesions were either homogenously Cx32-negative or showed unchanged to slightly elevated levels of Cx32 protein. There were no major differences in number and size distribution between lesions of these 2 phenotypes. In addition, larger lesions were mostly Cx32-negative but often contained embedded patches of Cx32-positive cells. Staining for the proliferation-associated nuclear antigen Ki-67 did not reveal significant differences between Cx32-negative and Cx32-positive hepatocytes in Cx32-mosaic tumors. This suggests that expression of Cx32 within a subpopulation of tumor cells does not negatively regulate their growth nor does it seem to affect the proliferation of their directly neighboring Cx32-negative counterparts. [source]


    Type-specific roles of histone deacetylase (HDAC) overexpression in ovarian carcinoma: HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration with downregulation of E-cadherin

    INTERNATIONAL JOURNAL OF CANCER, Issue 6 2010
    Akiko Hayashi
    Abstract Histone acetylation/deacetylation controls chromatin activity and subsequent gene transcription. Recent studies demonstrated the activation of histone deacetylases (HDACs) in various human malignancies; however, the expression and function of HDACs in ovarian tumors are not fully understood. In this study, we examined the immunohistochemical expression of HDAC1, HDAC2 and HDAC3 using tissues obtained from 115 cases of ovarian tumors and compared it with that of Ki-67 (a growth marker), p21, and E-cadherin and clinicopathological parameters. In addition, we analyzed the effect of specific siRNA for HDAC1, HDAC2 and HDAC3 on the expression of cell cycle-related molecules and E-cadherin to clarify the functional difference among the 3 HDACs. The results indicated that the immunohistochemical expression of nuclear HDAC1, HDAC2 and HDAC3 proteins increased stepwise in benign, borderline and malignant tumors. The expression of HDAC1 and HDAC2 was correlated with Ki-67 expression and that of HDAC3 was inversely correlated with E-cadherin expression. Among the HDACs examined, only HDAC1 was associated with a poor outcome, when overexpressed. Treatment with HDAC inhibitors suppressed the proliferation of ovarian cancer cells in association with apoptosis. A specific siRNA for HDAC1 significantly reduced the proliferation of ovarian carcinoma cells via downregulation of cyclin A expression, but siRNA for HDAC3 reduced the cell migration with elevated E-cadherin expression. Our results suggested that HDAC1 plays an important role in the proliferation of ovarian cancer cells, whereas HDAC3 functions in cell adhesion and migration. Therefore, specific therapeutic approaches should be considered according to the HDAC subtypes. [source]


    Biological aggressiveness of prostate cancer in the Finnish screening trial

    INTERNATIONAL JOURNAL OF CANCER, Issue 3 2009
    Marita Laurila
    Abstract Prostate cancer aggressiveness was evaluated based on pathologic characterization of cases detected in the Finnish prostate cancer screening trial. The trial population consists of 80,458 men aged 55,67 years. A total of 32,000 men were randomized to the screening arm. The remaining 48,000 men formed the control arm. The interval cases and cancers among nonparticipants and in the control arm were identified from the Finnish Cancer Registry. Random samples were selected from screen-detected cases (126 of 543 in the first and 133 of 508 in the second round) and control arm cancers (133 out of 863), in addition to all 92 interval cancers and 106 cases among nonparticipants. All the biopsies were regraded according to the Gleason system. The expression of the proliferation antigen Ki-67 was determined in 479 cases (72%). More than half of the tumors diagnosed in the first round of screening were high-grade cancers (Gleason 7 or higher). In the second round, the proportion of low-grade cancers increased from 47% to 70%. Cancers in the screening arm were more commonly focal and fewer bilateral cancers were detected. The cancers among nonparticipants were the most aggressive group. The aggressiveness of the interval cancers was between the cancers detected in the first and the second round. Our results indicate that prostate cancers detected through screening are less biologically aggressive. This was most notable after the first screening round. Nonparticipants had more aggressive cancers. © 2008 Wiley-Liss, Inc. [source]


    Immunohistochemical patterns in rectal cancer: Application of tissue microarray with prognostic correlations

    INTERNATIONAL JOURNAL OF CANCER, Issue 6 2004
    Eva Fernebro
    Abstract We utilized the high-throughput tissue microarray method to characterize immunohistochemical expression patterns with correlations to prognosis in rectal cancer. Immunostaining for the markers Ki-67, Bcl-2, p53, EGFR, E-cadherin, ,-catenin, MLH1 and MSH2 was performed in 269 rectal cancers. Expression profiles were correlated to metastasis-free survival. Immunostaining revealed frequent upregulation and/or aberrant staining patterns for several of the markers, but Ki-67, p53, Bcl-2 and EGFR did not show any correlation to prognosis. However, reduced membranous staining for ,-catenin (p = 0.04), lack of cytoplasmic staining for ,-catenin (p = 0.04), reduced membranous staining for E-cadherin (p = 0.02) and lack of cytoplasmic staining for E-cadherin (p = 0.02) correlated with metastatic disease. Multivariate analysis including the factors Dukes' stage and tumor differentiation grade demonstrated increased risk of metastatic disease in tumors with lack of cytoplasmic staining for ,-catenin (HR = 3.1, p = 0.02), reduced membranous staining for ,-catenin (HR = 1.7, p = 0.06) and reduced membranous staining for E-cadherin (HR = 2.1, p = 0.06). Loss of MMR protein expression was confirmed to be a rare event in rectal cancer with loss of MLH1 staining in 3% and MSH2 in 1% of the tumors. The lack of prognostic information contributed by most of these markers suggests that single markers for prognosis may be of limited value in rectal cancer. However, altered expression of ,-catenin and E-cadherin correlated with metastatic disease, and these markers may have prognostic importance in rectal cancer. © 2004 Wiley-Liss, Inc. [source]


    Biological characteristics of breast cancer at the primary tumour and the involved lymph nodes

    INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2005
    E. Dikicioglu
    Summary Diminished oestrogen receptor (ER) expression in the involved axillary lymph nodes (ALN) in breast cancer compared with the primary tumour has been reported in previous studies. We have assessed a wider spectrum of tumour markers (ER, progesterone receptor (PgR), p53, Ki-67 and HER-2/neu) and compared extent and staining intensities at the primary tumour and the involved ALN on specimens of 22 cases with invasive ductal breast cancer. At the involved ALN, both the quantity of positive staining cells and the staining intensities for ER and PgR were decreased (p < 0.001 and p = 0.003, respectively). In contrast, the quantity of positive staining cells (p < 0.004) and the staining intensities for Ki-67 were increased. The differences for HER-2/neu and p53 staining at both sites were insignificant. The immunohistochemical staining properties of both the primary tumour and the ALN metastases showed no correlation with the number of involved ALN (p > 0.05). This study suggested that ALN metastasis might indicate a more unfavourable expression pattern of ER, PgR and Ki-67 in invasive ductal breast cancer. [source]


    The prognostic value of p53, Ki-67 and matrix metalloproteinases MMP-2 and MMP-9 in transitional cell carcinoma of the renal pelvis and ureter

    INTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2005
    SHUICHI KAMIJIMA
    Aim: To investigate the prognostic and predictive relevance of p53 protein, Ki-67 antigen, MMP-2 and MMP-9 in patients with transitional cell carcinoma (TCC) of the upper urinary tract. Methods: The expression of p53 protein, Ki-67 antigen, MMP-2 and MMP-9 was examined by immunohistochemistry in 69 patients with TCC of the upper urinary tract. Correlation of p53, Ki-67, MMP-2 and MMP-9 over-expression with conventional pathological parameters and patient survival was examined. Results: p53 over-expression was signi,cantly correlated with histological grade (P < 0.05), but not with pathological stage, vascular invasion, lymphatic invasion or lymph node metastasis. Ki-67 over-expression was signi,cantly correlated with stage, grade, lymphatic invasion and vascular invasion (P < 0.05). In survival analyses, Ki-67 over-expression was a signi,cant prognostic factor in the univariate analysis (P < 0.05), but it did not have a signi,cant impact on survival in the multivariate analysis. Ki-67 labeling index was a signi,cant prognostic factor in patients with a low p53 labeling index, but not in patients with a high p53 labeling index. Conclusion: Ki-67 over-expression is of prognostic value in TCC of the upper urinary tract, while p53, MMP-2 and MMP-9 are of limited value. [source]


    Apoptosis in prostate cancer: Bax correlation with stage

    INTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2005
    ZAHRA AMIRGHOFRAN
    Abstract Background:, Dysregulation of apoptosis may contribute to the process of prostate tumorigenesis by reducing the rate of cell death. Bcl-2 and bax are important molecules involved in the regulation of apoptosis. The aim of the present study is to examine apoptosis and related regulatory molecular markers in a group of Iranian patients with prostate cancer. Methods:, Paraffin-embedded tissues from 50 patients of prostate carcinoma were examined for the expression of bcl-2 antiapoptotic and bax proapoptotic markers and also proliferation marker, Ki-67, by immunohistochemistry. Detection of apoptotic cells was performed using TUNEL method. Correlation between apoptotic index, proliferation index and bcl-2 and bax expression with stage, pathological grade and Gleason score was determined. Results:, Apoptosis was detected in 12% of prostate cancers. No correlation was observed between apoptosis and differentiation status of carcinoma. Bcl-2 expression was detected in 21 of samples. A significant correlation between bcl-2 expression and Ki-67 staining index (r = 0.349, P = 0.012) was observed. High bax protein expression was shown in our study. We found a significant correlation between bax expression and stage of carcinoma (r = 0.388, P = 0.031), but not with the apoptosis index, suggesting the presence of a non-functional bax protein or the role of other proapoptotic molecules. Conclusion:, The patients in the present study showed a different pattern of apoptosis positivity compared to other reports. Bax expression may be a useful marker for prognosis of prostate cancer. [source]


    Proliferative activity and genetic changes in adrenal cortical tumors examined by flow cytometry, fluorescence in situ hybridization and immunohistochemistry

    INTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2005
    KOUSUKE TAKEHARA
    Abstract Background: To determine differences in biological features among different adrenal tumors, we investigated the DNA ploidy, numerical chromosomal aberration and proliferative activity in human adrenal cortical neoplasms. Methods: Our study included six adrenal cortical adenomas with Cushing syndrome, 12 adenomas with hyperaldosteronism, three non-functioning adenomas and three adrenal cortical carcinomas. Isolated nuclei from frozen samples were used for fluorescence in situ hybridization (FISH) analysis, and formalin-fixed, paraffin-embedded tissues from the same materials were analyzed using flow cytometry (FCM) for DNA ploidy. Sections from paraffin blocks were stained immunohistochemically with antibodies against Ki-67 and p53. For FISH analysis, we used an ,-centromeric enumeration probe for chromosome 17. Results: The mean Ki-67 labeling index (LI) of adrenal cortical carcinomas was markedly higher than that of adrenal cortical adenomas (209.4 vs 8.7). In functional adrenal cortical adenomas, the LI was significantly lower in adenomas with hyperaldosteronism than in those with Cushing syndrome (P = 0.004), although FCM results indicated that tetraploid patterns were more frequently observed in the former type. Tumor size was significantly smaller in adenomas with hyperaldosteronism than in those with Cushing syndrome (P = 0.004). Chromosome 17 showed disomy in all adrenal cortical adenomas, whereas chromosome 17 abnormalities were found in two of three adrenal cortical carcinomas. Only the latter two cases strongly expressed p53 protein. Conclusions: Our study characterized various biological features of benign and malignant adrenal cortical tumors. The use of a combination of markers might provide additional information to assist our understanding of the clinical behavior of an individual adrenal cortical tumor. [source]


    The effect of various concentrations of human recombinant epidermal growth factor on split-thickness skin wounds

    INTERNATIONAL WOUND JOURNAL, Issue 2 2006
    Article first published online: 19 JUN 200
    Effet de concentrations variées de facteur de croissance épidermique recombinant sur les plaies cutanées d'épaisseur partielle Le facteur de croissance épidermique (EGF) est un stimulant puissant de l'épithélialisation. Cependant, l'application topique d'EGF pour aider à la réépithélialisation des plaies d'épaisseur partielle reste sujette à controversies. Un total de 10 porcs, chacun soumis à une plaie dd'épaisseur partielle de 4 cm/4 cm ont été traités 2 fois par jour pendant 10 jours pour étudier les effets de l'EGF humain recombinant avec des concentrations de 0,1, 1, 5, 10, 20 ,g/g, l'excipient seul et deux groupes contrôles. Les plaies des groupes contrôles et de l'excipient seul ont obtenu un temps de cicatrisation à 100%(HT100) de 9·31 ± 1·34 et 8·5 ± 1·12 alors que les plaies traitées par la crème à l'EGF en concentration à 0·1 ,g/g (HT100 6·40·71), 1 ,g/g (HT100 5·2 ± 0·63), 5 ,g/g (HT100 5·8 ± 0·85), 10 ug/g (HT100: 7·1 ± 1·45), et 25 ug/g (HT100: 7·4 ± 0·57) ont démontré des reductions de temps d'épithélialisation significatives. Parmi les plaies traitées par EGF, les plaies traitées avec des concentrations de 1 et 5 ,g/g obtenaient les épithélialisations les plus rapides et démontraient une augmentation substantielle d'activité des kératinocytes de la couche basale observée par activié Ki-67. En conclusion, Cette etude démontre l'efficacité du facteur de croissance épidermique humain recombinant dans la réépithélialisation des plaies cutanées d'épaisseur partielle, l'effet étant maximum avec des concentrations en EGF de 1 et 5 ,g/g. Einfluß unterschiedlicher humaner rekombinanter epidermaler Wachstumsfaktoren auf intradermale Wunden Epidermal Growth Factor (EGF) ist ein potentes Stimulans für die Epithelialisierung. Es wird jedoch kontrovers diskutiert, ob die topische Applikation von EGF in interadermalen Wunden eine beschleunigte Wundheilung erzielt. 10 Schweine, die jeweils eine 4 × 4 cm intradermale Wunde erhielten, wurden zweimal täglich mit hr-EGF in den Konzentrationen 0,1, 1, 5, 10 und 25 ug über einen Zeitraum von 10 Tagen behandelt. Eine Wunde wurde lediglich mit dem Vehikel, eine weitere als Kontrollwunde behandelt. Diese beiden Wunden erreichten eine 10% Heilung (HT100) nach 9·31 ± 1·34 and 8·5 ± 1·12 Tagen. Dagegen zeigten die Wunden, die mit 0,1 ug HT100: 6·4 ± 0·71), 1 ug/g (HT100: 5·2 ± 0·63), 5 ug/g (HT100: 5·8 ± 0·85), 10 ug/g (HT100: 7·1 ± 1·45), and 25 ug/g (HT100: 7·4 ± 0·57) eine signifikant verkürzte Heilungsdauer. Innerhalb dieser unteschiedlichen Konzentrationen erwiesen sich die Konzentrationen 1 und 5 ug/g als am effektivsten, was durch die Ki-67 Aktivität gezeigt wurde. Zusammenfassend konnte gezeigt werden, dass der hr-EGF eine effektive Substanz für die Heilung von kutanen Wunden ist mit der höchsten Effektivität bei 1 und 5 ug/g. L'effetto di varie concentrazioni di fattore di crescita umano epidermico ricombinante su ulcere cutanee a spessore parziale Il fattore di crescita epidermico (EGF)è un potente stimolatore della riepitelizzazione. Tuttavia l'applicazione topica di EGF per ottenere una migliore riepitelizzazione in lesioni a spessore parziale è molto controversa. Sono stati trattati un totale di 10 maiali, ognuno con lesioni a spessore parziale di 4 × 4 cm, due volte al giorno per 10 giorni per osservare l'effetto del fattore umano ricombinante EGF in concentrazioni di 0·1, 1, 5, 10, 25 ug/g, del solo veicolo, in due controlli. Le ulcere controllo ed il veicolo hanno mostrato ciascuna un 100% di tempo di guarigione (HT100) di 9·31 ± 1·34 e 8·5 ± 1·12 mentre le lesioni trattate con EGF in unguento a concentrazione di 0·1 ug/g (HT100: 6·4 ± 0·71), 1 ug/g (HT100: 5·2 ± 0·63), 5 ug/g (HT100: 5·8 ± 0·85). 10 ug/g (HT100: 7·1 ± 1·45), e 25 ug/g (HT100: 7·4 ± 0·57) hanno mostrato una significativa riduzione del tempo di guarigione. Tra le lesioni trattate con EGF, le lesioni trattate con concentrazioni di EGF di 1 e 5 ug/g hanno ottenuto la più veloce riepitelizzazione con evidenza di un sostanziale incremento nella attività dei cheratinociti basali osservata attraverso l'attività del Ki-67. In conclusione, questo report dimostra l'efficacia del fattore di crescita umano ricombinante epidermico nel favorire la riepitelizzazione di lesioni a spessore parziale con la migliore applicazione di EGF alle concentrazioni di 1 e 5 ug/g. Efecto de diversas concentraciones del factor de crecimiento epidérmico recombinante humano sobre heridas cutáneas de espesor parcial El factor de crecimiento epidérmico (FCE) es un potente estimulante de la epitelización. No obstante, subsiste un debate sobre la aplicación tópica del FCE para facilitar la reepitelización en heridas de espesor parcial. Se trató a un total de diez cerdos, cada uno con ocho heridas de espesor parcial de 4 × 4 cm, dos veces al día durante 10 días para observar el efecto del FCE recombinante humano a concentraciones de 0,1, 1, 5, 10, 25 ,g/g, el vehículo solo y dos controles. Las heridas de control y las tratadas exclusivamente con el vehículo presentaron un tiempo de curación del 100%(TC100) de 9,31 ± 1,34 y 8,5 ± 1,12, mientras que las heridas tratadas con la pomada de FCE a concentraciones de 0,1 ,g/g (TC100: 6,4 ± 0,71), 1 ,g/g (TC100: 5,2 ± 0,63), 5 ,g/g (TC100: 5,8 ± 0,85), 10 ,g/g (TC100: 7,1 ± 1,45) y 25 ,g/g (TC100: 7,4 ± 0,57) mostraron una reducción significativa del tiempo necesario para conseguir la reepitelización. De las heridas tratadas con FCE, en las que recibieron las concentraciones de 1 y 5 ,g/g se logró una reepitelización más rápida con, signos de incremento considerable de la actividad basal de los queratinocitos observada por medio de la actividad Ki-67. En conclusión, este trabajo demuestra la eficacia del factor de crecimiento epidérmico recombinante humano en facilitar la reepitelización de heridas de espesor parcial, y que la curación más eficiente se obtiene con concentraciones de FCE de 1 y 5 ,g/g. Effekten av varierande koncentrationer av human rekombinant epidermal tillväxtfaktor på delhudssår Epidermala tillväxtfaktorn (EGF)är en potent stimulant av epitelialisering. Topisk applicering av EGF för att befrämja re-epitelialisering av delhudssår har emellertid varit kontroversiellt. Totalt 10 grisar, alla med åtta 4 × 4 cm delhudssår, behandlades två gånger dagligen under 10 dagar för att observera effekten av "human recombinant EGF" i koncentrationer av 0·1, 1, 5, 10, 25 ug/g, vehikel enbart, och två kontroller. Vart och ett av kontroll och vehikel enbart såren uppvisade 100% läkningstid (HT100) på 9·31 ± 1·34 och 8·5 ± 1·12, medan de sår som behandlades med EGF salva med en koncentration av 0·1 ug/g (HT100: 6·4 ± 0·71), 1 ug/g (HT100: 5·2 ± 0·63), 5 ug/g (HT100: 5·8 ± 0·85), 10 ug/g (HT100: 7·1 ± 1·45), och 25 ug/g (HT100: 7·4 ± 0·57) uppvisade signifikant reduktion av tiden för att uppnå re-epitelialisering. Bland de EGF behandlade såren, uppnådde de sår som behandlats med EGF med en koncentration av 1 och 5 ug/g snabbast re-epitelialisering med bevis för märkbar ökning av basal keratinocyte aktivitet iakktagen genom Ki-67 aktivitet. Sammanfattningsvis uppvisar denna rapport den gynnsamma effekten av human rekombinant EGF i re-epitelialisering av delhuds sår. Den gynnsammaste läkningseffekten iakktogs med EGF i koncentrationer av 1 och 5 ug/g. [source]


    Assessment of "grading" with Ki-67 and c-kit immunohistochemical expressions may be a helpful tool in management of patients with flat epithelial atypia (FEA) and columnar cell lesions (CCLs) on core breast biopsy

    JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2009
    Rosa M. Tomasino
    It is essential to reach a better understanding of "flat epithelial atypia/columnar cell lesions" (FEA/CCLs) in breast core biopsies. Our aim was to explore their biological nature, in order to predict the likelihood of an upgrade to carcinoma. "Cytological grading" has been specially focused, in view of its possible utility in the choice of management. One hundred thirty of a total of 900 cases core needle (CN)/vacuum-assisted biopsies (VABs), with diagnoses of "hyperplasia" and "atypia" were retrospectively re-evaluated. Pathological findings of further excision biopsies (FEBs) performed in 40/75 patients with follow-up were compared with the previous diagnoses. In all cases, both Ki-67 and c-kit immunoreactivities were explored and compared with both normal breast tissues and subsequently documented cancers, with special reference to the hyperplastic FEA/CCLs, with "mild" atypia (FEA/CCHAm). Sixteen cases were re-diagnosed as "usual ductal hyperplasia" (UDH), 60 as "columnar cell hyperplasia" (CCH), and 54 as FEA/CCHA, 30 of which FEA/CCHAm and 24 FEA/CCHAh (with high atypia). Significantly, the Ki-67 index proved to be on the increase and c-kit expression on the decrease in FEA/CCHA lesions, mainly in the FEA/CCHAh group and in the subsequently observed cancers, compared with either benign tissues or the FEA/CCH cases. It was also significant that most of the carcinomas were found in FEBs within the FEA/CCHAh group. In this study cytological grading, together with Ki-67 and c-kit indices, proved to be helpful in FEA/CCLs evaluation. With regard to FEA/CCHAm lesions, an adequate surveillance appears to be a more appropriate management tool than FEB, as a result of their biological nature and behavior. J. Cell. Physiol. 221: 343,349, 2009. © 2009 Wiley-Liss, Inc. [source]


    Involvement of IQGAP3, a regulator of Ras/ERK-related cascade, in hepatocyte proliferation in mouse liver regeneration and development,

    JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2009
    Koshi Kunimoto
    The spatio-temporal regulation of hepatocyte proliferation is a critical issue in liver regeneration. Here, in normal and regenerating liver as well as in developing liver, we examined its expression/localization of IQGAP3, which was most recently reported as a Ras/Rac/Cdc42-binding proliferation factor associated with cell,cell contacts in epithelial-type cells. In parallel, the expression/localization of Rac/Cdc42-binding IQGAP1/2 was examined. IQGAP3 showed a specific expression in proliferating hepatocytes positive for the proliferating marker Ki-67, the levels of expressions of mRNAs and proteins were significantly increased in hepatocytes in liver regeneration and development. In immunofluorescence, IQGAP3 was highly enriched at cell,cell contacts of hepatocytes. IQGAP1 and IQGAP2 were exclusively expressed in Kupffer and sinusoidal endothelial cells, respectively, in normal, regenerating, and developing liver. The expression of IQGAP1, but not of IQGAP2, was increased in CCl4 -induced (but not in partial hepatectomy-induced) liver regeneration. Exclusive expression/localization of IQGAP3 to hepatocytes in the liver likely reflects the specific involvement of the IQGAP3/Ras/ERK signaling cascade in hepatocyte proliferation in addition to the previously identified signaling pathways, possibly by integrating cell,cell contact-related proliferating signaling events. On the other hand, the Rac/Cdc42-binding properties of IQGAP1/2/3 may be related to the distinct modes of remodeling due to the different strategies which induced proliferation of liver cells; partial hepatectomy, CCl4 injury, or embryonic development. Thus, the functional orchestration of Ras and the Ras homologous (Rho) family proteins Rac/Cdc42 likely plays a critical role in liver regeneration and development. J. Cell. Physiol. 220: 621,631, 2009. © 2009 Wiley-Liss, Inc. [source]


    Giant clear cell hidradenoma of the knee

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2010
    Gengsheng Yu
    Hidradenomas, also referred to as nodular hidradenomas or clear cell hidradenomas (CCH), are benign cutaneous eccrine tumors usually 2,3 cm in dimension. Hidradenomas are relatively common; however, giant forms are rare. We report a case of an 8.0 × 6.0 × 3.0 cm clear cell hidradenoma of the left knee in a 43-year-old man. The tumor was mobile, located above the patellar tendon and was without bony involvement on imaging studies. Grossly, the resected tumor was unencapsulated and tan, with a solid and cystic cut surface showing papillary excrescences on the cyst wall. Microscopically, the tumor cells showed an infiltrative growth pattern at the periphery, however, the tumor cytology was bland and no necrosis or mitoses were identified. The overlying dermis contained hemosiderin pigment deposition and infiltration with eosinophils. Immunohistochemically, tumor cells were positive for cytokeratin, CAM5.2, p53, carcino-embryonic antigen (CEA) and epithelial membrane antigen (EMA), and negative for CD10 and Ki-67. The cytological features of hidradenomas can present diagnostic challenges, as other ,clear cell' tumors such as metastatic renal cell carcinoma should be considered. Immunohistochemical studies and differential diagnoses are discussed. Yu G, Goodloe S, D'Angelis CA, McGrath BE, Chen F. Giant clear cell hidradenoma of the knee. [source]


    G1 cell cycle regulators in congenital melanocytic nevi.

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2008
    Comparison with acquired nevi, melanomas
    Background:, Congenital nevi are one of the known risk factors for the development of melanoma. However, the magnitude of the risk for both large and small congenital nevi is controversial. Methods:, In order to elucidate the behavior of congenital nevocytes and to define any possible similarities or differences with common nevi and melanomas, we investigated the expression of Ki-67, Rb, p16, cyclin D1, p53 and p21/Waf-1 in 41 congenital nevi, 16 melanomas and 20 acquired common nevi by immunohistochemistry. Results:, Congenital nevi highly expressed p16 (81.82 ± 9.98) but showed limited, if any, reactivity for Ki-67 (1.34% ± 0.89), Rb (0.76% ± 0.94), cyclin D1 (0.21% ± 0.29), p53 (0.54% ± 0.93) and p21 (0.0609% ± 0.32). No statistically significant difference was found between giant and nongiant congenital nevi and between congenital and common nevi for any of the markers. The expression of p16 was significantly higher in congenital nevi than in melanomas (p < 0.0001). On the contrary, the expression of Ki-67, p53, p21, Rb and cyclin D1 was significantly higher in melanomas (p < 0.0001). Conclusion:, Our data regarding the immunohistochemical expression of Rb, p16, p53, cyclin D1 and Ki-67 in congenital nevi indicate that either the alteration of their expression is not an initiating event in melanoma formation or, alternatively, congenital melanocytic nevi may not be the first step in malignant transformation. [source]


    The effects of gp100 and tyrosinase peptide vaccinations on nevi in melanoma patients

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 5 2006
    David S. Cassarino
    Background:, A new approach to prevent disease recurrence in high-risk melanoma patients involves immunization with gp100 and tyrosinase peptides. This is the first study to examine the effects of such treatments on nevi. Design:, We studied biopsies of ,clinically atypical' nevi from 10 patients before and after peptide vaccination. All had a cutaneous melanoma measuring at least 1.5 mm in depth, satellite metastases, or at least one positive lymph node. We performed immunohistochemical stains for CD3, CD4, CD8, MHC-I, MHC-II, CD1a, HMB-45, MART-1, tyrosinase, bcl-2, p53, and Ki-67 (mib-1). Results:, Immunohistochemistry showed no differences in staining due to vaccination in either the immunologic or melanocytic markers. However, there was a significant increase in both p53 and bcl-2 staining, and a trend toward decreased Ki-67 staining, in the nevi post-treatment. Discussion:, The primary goal of peptide vaccinations with gp100 and tyrosinase is to activate melanoma-specific T cells in order to prevent melanoma recurrence. Nevi were studied in order to assess the effects on benign melanocytes. No significant changes in lymphocytes, langerhans cells, expression of MHC antigens, or melanocytic markers were found. The increase in p53 and bcl-2 raises the possibility that vaccination with melanocytic antigens stimulates a response in benign melanocytes. [source]


    p63 expression in normal human epidermis and epidermal appendages and their tumors

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2003
    Miki Tsujita-Kyutoku
    Background:, p63, a member of the p53 gene family, is expressed in basal cells of several different organs. Methods:, The immunoreactivity of p63 was examined in normal human epidermis and epidermal appendages and their tumors, and compared with proliferative activity as evaluated by Ki-67. Results:, In normal skin, p63 expression was seen in basal/suprabasal cells of the epidermis, outer root sheath and hair matrix cells of the hair follicle, seboblast situated in the outermost layer of sebaceous glands, and outer layer cells of the ductal portion and myoepithelial cells of the secretory portion of the sweat glands. p63 expression was confined to the cells forming a continuous basal rim along the normal epithelial structure. In tumors, p63 expression resembled that in normal tissue in that tumor components originating from p63-positive cells were constantly positive for p63. In normal and tumor tissues, not all p63-positive cells were positive for Ki-67. Conclusions:, p63 expression may be a marker of basal/progenitor cells in tumors of epidermis and epidermal appendages, and may be a diagnostic marker of these tumors. [source]


    Combined histology and molecular biology for diagnosis of early stage gastric MALT lymphoma

    JOURNAL OF DIGESTIVE DISEASES, Issue 1 2006
    Zhi Hui YI
    OBJECTIVE: To establish a sequential diagnostic procedure of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and provide evidence for selected optimal cases to be treated in the early stage. METHODS: Thirty-one cases of gastric lymphoid hyperplasia (GLH) were selected and multiple investigations including histology, protein level, DNA and chromosome levels, combined with clinical follow-up were performed. Histological grade was according to Isaacson's criteria of GLH; CD20, UCHL-1 (CD45RO), anti-kappa (,), anti-lambda (,) and Ki-67 were used for immunohistochemical staining; semi-nested polymerase chain reaction (PCR) was used to detect IgH gene rearrangement and reverse-transcription PCR (RT-PCR) was used to detect API2-MALT1 fusion of the chromosome translocation t(11;18)(q21;q21). Twenty-nine cases underwent eradication therapy for Helicobacter pylori. Changes in histological grade, endoscopic appearance, expression of Ki-67 and IgH gene rearrangement were compared after eradication treatment. RESULTS: Of the 31 cases of GLH with predominant chronic gastritis and gastric ulcer most were histological grade 2 and 3. Only one case had , light chain restriction and 10 cases had monoclonal IgH gene rearrangement. Expression of Ki-67 and monoclonal IgH gene rearrangement were significantly increased with increased lymphoid hyperplasia (P < 0.05). Two cases had API2-MALT1 fusion. Helicobacter pylori was eradicated in 25 cases and another course of treatment had to be given in 4 cases. All cases were followed up for 1.5,37 months. Of the 27 successful eradication cases, 18 showed complete regression both histologically and endoscopically, 4 had partial regression and 7 were unchanged. CONCLUSIONS: A sequential diagnostic procedure based on histology, expression of Ki-67 combined with clonality of IgH rearrangement and API2-MALT1 fusion helps to diagnosis of early stage gastric MALT lymphoma and choose the best treatment strategy. [source]


    Effect of aging on neurogenesis in the canine brain

    AGING CELL, Issue 3 2008
    Anton Pekcec
    Summary An age-dependent decline in hippocampal neurogenesis has been reported in laboratory rodents. Environmental enrichment proved to be a strong trigger of neurogenesis in young and aged laboratory rodents, which are generally kept in facilities with a paucity of environmental stimuli. These data raise the question whether an age-dependent decline in hippocampal cell proliferation and neurogenesis can also be observed in individuals exposed to diversified and varying surroundings. Therefore, we determined rates of canine hippocampal neurogenesis using post-mortem tissue from 37 nonlaboratory dogs that were exposed to a variety of environmental conditions throughout their life. Expression of the neuronal progenitor cell marker doublecortin clearly correlated with age. The analysis of doublecortin-labeled cells in dogs aged > 133 months indicated a 96% drop in the aged canine brain as compared to young adults. Expression of the proliferation marker Ki-67 in the subgranular zone decreased until dogs were aged 85,132 months. In the aging canine brain amyloid-beta peptide deposits have been described that might resemble an early pathophysiological change in the course of human Alzheimer's disease. Comparison of Ki-67 and doublecortin expression in canine brain tissue with or without diffuse plaques revealed no differences. The data indicate that occurrence of diffuse plaques in the aging brain is not sufficient to trigger enhanced proliferation or enhanced neurogenesis such as described in human Alzheimer's disease. In addition, this study gives first proof that an age-dependent decline also dominates hippocampal neurogenesis rates in individuals living in diversified environments. [source]


    Differential Effects of Stress on Adult Hippocampal Cell Proliferation in Low and High Aggressive Mice

    JOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2007
    A. H. Veenema
    Male wild house mice selected for a long (LAL) or a short (SAL) latency to attack a male intruder generally show opposing behavioural coping responses to environmental challenges. LAL mice, unlike SAL mice, adapt to novel challenges with a highly reactive hypothalamic-pituitary-adrenal axis and show an enhanced expression of markers for hippocampal plasticity. The present study aimed to test the hypothesis that these features of the more reactive LAL mice are reflected in parameters of hippocampal cell proliferation. The data show that basal cell proliferation in the subgranular zone (SGZ) of the dentate gyrus, assessed by the endogenous proliferation marker Ki-67, is lower in LAL than in SAL mice. Furthermore, application of bromodeoxyuridine (BrdU) over 3 days showed an almost two-fold lower cell proliferation rate in the SGZ in LAL versus SAL mice. Exposure to forced swimming resulted, 24 h later, in a significant reduction in BrdU + cell numbers in LAL mice, whereas cell proliferation was unaffected by this stressor in SAL mice. Plasma corticosterone and dentate gyrus glucocorticoid receptor levels were higher in LAL than in SAL mice. However, no differences between the SAL and LAL lines were found for hippocampal NMDA receptor binding. In conclusion, the data suggest a relationship between coping responses and hippocampal cell proliferation, in which corticosterone may be one of the determinants of line differences in cell proliferation responses to environmental challenges. [source]


    Clinicopathological features and immunohistochemical expression of p53, Ki-67, Mcm-2 and Mcm-5 in proliferative verrucous leukoplakia

    JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 6 2010
    Adriele Ferreira Gouvêa
    J Oral Pathol Med (2010) 39: 447,452 Background:, Proliferative verrucous leukoplakia (PVL) is a distinct and aggressive type of oral leukoplakia which affects elderly women without risk behavior and presents high rates of malignant transformation. The objective of the present study was to evaluate the clinicopathological characteristics and the distribution of cell proliferation markers, aiming to elucidate the distinct biological behavior of the PVL. Methods:, Clinical and microscopical features of 12 patients with PVL were reviewed. Immunohistochemical analysis for p53, Ki-67, Mcm-2 and Mcm-5 were performed and the data were correlated. Results:, All patients were women, above 50 years of age, 91.7% were non-smoker and 100% were non-habitual drinker. Alveolar ridge (66.6%), tongue (50%) and buccal mucosa (41.6%) were the most affected sites. Four patients developed squamous cell carcinoma (SCC). The immunohistochemical findings showed higher positivity for p53, Ki-67, Mcm-2 and Mcm-5 in SCCs. However, some patients with mild or moderate dysplasia, specially the patients who developed SCC, presented high expression of Mcm-2 and Mcm-5. Conclusions:, High immunoexpression of Mcm-2 and Mcm-5 in mild and moderate dysplasia could be helpful to predict the malignant transformation of PVL. [source]


    Plasmablastic lymphomas with light chain restriction , plasmablastic extramedullary plasmacytomas?

    JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 5 2010
    Sonja C. Boy
    J Oral Pathol Med (2010) 39: 435,439 Background:, It is diagnostically difficult to differentiate plasmablastic lymphomas (PBLs) from plasma cell neoplasms with plasmablastic differentiation. Plasmablastic lymphomas are currently classified as ,PBL of the oral mucosa' and ,PBL with plasmacytic differentiation'. Methods:, Forty-five cases of PBL were retrieved from the Departments of Oral Pathology of the Universities of Pretoria and Limpopo, South Africa. Clinical features and HIV status were recorded and each case was classified as ,PBL of the oral mucosa type' or as ,PBL with plasmacytic differentiation'. Immunohistochemistry included: CD45, CD3, CD20, CD79a, CD38, CD138, MUM1, Ki-67 and kappa and lambda light chains. Positivity was recorded based on the percentage of positive staining cells as focal (5,20%); intermediate (20,70%) or diffuse (>70%). In situ hybridization was performed for Epstein,Barr virus (EBV) and HHV-8. Results were recorded as positive or negative. Results:, All cases showed some degree of plasmacytic differentiation. All were negative for CD20 with reactive T cells detected with CD3. Diffuse and strong positive staining was found with Ki-67 and MUM1, but variable immunoreactivity was found with CD79a, CD45, CD38 and CD138. Twenty cases (47%) showed light chain restriction. Epstein,Barr virus was detected in 44/45 cases and HHV-8 in none. Conclusions:, The morphological classification of PBLs is not valid as all cases showed some degree of plasmacytic differentiation. We propose that PBLs with light chain restriction be reclassified as ,plasmablastic extramedullary plasmacytomas' and managed accordingly. The rest represents true PBLs. The true nature of these neoplasms as an entity should be further investigated with molecular and genetic studies. [source]


    Angiogenic and lymphangiogenic microvessel density in recurrent pleomorphic adenoma

    JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2009
    Andresa B. Soares
    Background:, Recurrent pleomorphic adenoma (RPA) is an uncommon and challenging disease. The aim of this study was to determine if there is a difference between RPA and the pleomorphic adenoma (PA) without recurrence related to tumor blood and lymphatic vascularization. Moreover, we compared the microvessel density (MVD) between cell-rich areas (predominance of epithelial cells) and cell-poor areas (predominance of myxoid and chondroid areas) of the stroma of PA and RPA. In addition, immunohistochemical staining for the Ki-67 antigen was conducted simultaneously to evaluate cell proliferation in PA and RPA. Methods:, A total of 19 cases of PA and 24 cases of RPA, blood, and lymphatic vessels were analyzed by immunohistochemical technique using the antibodies CD34, CD105, D2-40, and Ki-67. Results:, Comparing no recurrent with recurrent tumor, no significant difference was found in terms of lymphatic vessel density, MVD, and proliferation index. When MVD and proliferation index were compared with different areas in cellular composition (cell-rich and cell-poor areas), there was a significant difference in PA, as well as in RPA. Conclusion:, This study shows that although RPA presents more aggressive clinical behavior than PA, there is no difference between tumor blood and lymphatic vascularization, suggesting that there is no correlation between vascularity and risk of recurrence. Furthermore, vascularized stroma in PA, as well as RPA, depends on the proportion of the cellular composition. [source]


    Immunohistochemical analysis of the biological potential of odontogenic keratocysts

    JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 2 2006
    k Kolá
    Background:, The aim of this study was to analyse the usefulness of detecting important apoptosis and proliferation markers in assessing the biological potential of odontogenic keratocysts (OKC) and thus selecting the optimal diagnostic algorithm for these lesions. Methods:, Indirect immunohistochemistry and relevant statistical methods were used for analysis of formalin-fixed and paraffin-embedded samples from 98 patients. Results:, Nevoid basal cell carcinoma syndrome (NBCCS) keratocysts were characterized by higher expression of Bcl-2, p27Kip1 and c-erbB-2 as well as by lower proliferative activity measured by Ki-67 in basal cell epithelium and by a lower inflammatory response in comparison with sporadic keratocysts. Dentigerous, radicular and non-specified odontogenic cysts differed from both NBCCS and sporadic keratocysts in a wide spectrum of apoptosis and/or cell cycle-related protein expressions, higher proliferation in the basal cell layer, and vice versa, lower proliferation in the suprabasal cell layer. Conclusions:, The NBCCS keratocysts have a different immunophenotype from sporadic keratocysts and both types are distinguishable from dentigerous, radicular and non-specified odontogenic cysts. These findings confirm the separate biological potential of these lesions and the results of the immunohistochemical analysis have diagnostic and prognostic implications. [source]


    Immunohistochemical study of syndecan-1 down-regulation and the expression of p53 protein or Ki-67 antigen in oral leukoplakia with or without epithelial dysplasia

    JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2003
    Hideo Kurokawa
    Abstract Background:, Leukoplakia is an oral pre-cancerous lesion that sometimes develops into squamous cell carcinoma. Therefore, leukoplakia with epithelial dysplasia is useful for studying carcinogenesis at the cellular level. The purpose of this study was to evaluate a potential association between the loss of syndecan-1 expression and the expression of p53 protein and Ki-67 antigen, and to identify reliable markers for predicting malignant changes in oral leukoplakia with epithelial dysplasia. Methods:, Changes in the expression of syndecan-1, p53, and Ki-67 were examined immunohistochemically in 43 cases of oral leukoplakia with or without epithelial dysplasia. The subjects were categorized as: none, 13 cases; mild dysplasia, 5 cases; moderate dysplasia, 17 cases; and severe dysplasia, 8 cases. The expression of these molecules in normal oral epithelia (22 cases) was also investigated. Results:, Strong syndecan-1 expression was observed on the surface of keratinocytes in normal epithelium. Immunopositivity was lost gradually as the extent of epithelial dysplasia increased. In normal epithelium, p53 and Ki-67 appeared mainly in the basal cell layer, while they were more widely distributed in leukoplakia. Specifically, significant changes were observed in the labeling index of p53 and Ki-67 in leukoplakia as epithelial dysplasia progressed from mild to moderate or severe. Conclusion:, Our results reveal that overexpression of p53 protein and Ki-67 antigen, and down-regulation of syndecan-1 expression in the lower part of the epithelium, are associated with dysplastic changes. Therefore, the down-regulation of syndecan-1 expression may be the most important reliable marker for dysplastic changes. [source]