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Labeling Index (labeling + index)
Kinds of Labeling Index Selected AbstractsMIB-1 immunolabeling: A valuable marker in prediction of benign recurring meningiomasNEUROPATHOLOGY, Issue 5 2007Mahesha Vankalakunti Histological analysis has limited value to predict biological behavior of meningiomas. We investigated the utility of cell proliferative indicator in the evaluation of histologically benign meningiomas. We selected 25 benign non-recurrent meningiomas, 15 benign recurrent meningiomas after complete surgical resection, 30 atypical meningiomas, and 15 anaplastic meningiomas out of 384 cases studied. MIB-1 Labeling Index was evaluated by two methods: Highest Labeling Index (HLI) and Random Labeling Index (RLI). There was no dependable histological parameter to predict recurrence among benign-looking meningiomas. HLI had significant difference when compared with RLI in all categories. The mean MIB-1 HLI values ± SD were 3.47 ± 2.0% for benign meningiomas, 5.08 ± 4.0% for atypical meningiomas and 11.66 ± 7.06% for anaplastic meningiomas. In comparison, the mean MIB-1 HLI of benign non-recurrent meningiomas were 2.66 ± 1.7% and with recurrence were 4.21 ± 2.78% (P = 0.0339). Using receiver operating characteristic, it was seen that neoplasm recurred with the MIB-1 HLI of > 2.6 having the sensitivity of 64.6% and specificity of 68% among benign (grade I) meningiomas. MIB-1 positive tumor cells were maximally aggregated at the periphery of excised specimen. MIB-1 HLI, integrated with standard histopathology can provide better information about the disease biological nature in benign meningiomas. [source] Cell proliferation and differentiation during fracture healing are influenced by locally applied IGF-I and TGF-,1: Comparison of two proliferation markers, PCNA and BrdUJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2003B. Wildemann Abstract Growth factors IGF-I and TGF-,1 are known to stimulate fracture healing. The purpose of this study was to investigate the role of locally applied IGF-I and TGF-,1 during the early phase of fracture healing (Days 5, 10, and 15 after fracture) on cellular processes like proliferation and differentiation in a rat model. Two different immunohistochemical markers were used to analyze cell proliferation: (1) injection of the thymidine analogue BrdU and subsequent immunohistochemical staining for BrdU-positive nuclei, and (2) the antibody against the "proliferating cell nuclear antigen" (PCNA). In comparison, both methods revealed similar results concerning the types of proliferating cells at the different time points and the two groups. Labeling indices of both methods showed very good correlation (e.g., rs: 0.887 and p < 0.001 at day 10 in the control group without growth factors). Comparison of the callus morphology and the proliferation rate showed differences during fracture healing due to the local application of IGF-I and TGF-,1 from coated implants. At Day 5 the callus of the group treated with growth factors displayed an earlier appearance of cartilage compared to the control group. This was accompanied by an onset of cell proliferation in chondrocytes. Likewise, at the later time points an enhanced maturation of the callus tissue and the proliferation pattern were detectable in the growth-factor group. These results indicate that local application of IGF-I and TGF-,1 accelerates early cellular processes during fracture healing. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 65B: 150,156, 2003 [source] Homocysteine inhibits cardiac neural crest cell formation and morphogenesis in vivoDEVELOPMENTAL DYNAMICS, Issue 1 2004Brent J. Tierney Abstract Elevated homocysteine increases the risk of neurocristopathies. Here, we determined whether elevating homocysteine altered the proliferation or number of chick neural crest cells that form between the midotic and third somite in vivo. Homocysteine increased the number of neural tube cells but decreased neural crest cell number. However, the sum total of cells was not different from controls. In controls, the 5-bromo-2,-deoxyuridine-labeling index was higher in newly formed neural crest cells than in their progenitors, paralleling reports showing these progenitors must pass the restriction point before undergoing epithelial,mesenchymal transition. Homocysteine decreased the labeling index of newly formed neural crest cells, suggesting that it inhibited cell cycle progression of neural crest progenitors or the S-phase entry of newly formed neural crest cells. Homocysteine also inhibited neural crest dispersal and decreased the distance they migrated from the neural tube. These results show neural crest morphogenesis is directly altered by elevated homocysteine in vivo. Developmental Dynamics 229:63,73, 2004. © 2003 Wiley-Liss, Inc. [source] Cytologic feature by squash preparation of pineal parenchyma tumor of intermediate differentiationDIAGNOSTIC CYTOPATHOLOGY, Issue 10 2008Keiji Shimada M.D., Ph.D. Abstract Pineal parenchyma tumor of intermediate differentiation (PPTID) is a very rare intracranial tumor, and pathological investigation limited to immunohistological and ultrastructural analyses have been published to date. Although intraoperative cytology is one of the important approaches for initial diagnosis in brain tumors, no or little studies on cellular morphology of PPTID have been demonstrated due to its rarity. We report here cytological features of PPTID obtained from stereotactic surgical specimens in a case of 27-year-old female manifested by dizziness and diplopia. Brain MRI revealed an unhomogeneously enhanced, large-sized tumor (56 × 52 × 60 mm) mainly located in the pineal region expanding from the midbrain to superior portion of the cerebellum and the fourth ventricle. Squash cytology showed increased nucleocytoplasmic ratio, hyperchromatic nuclei, and small rosette-like cell cluster but cellular pleomorphism was mild to moderate and necrotic background was not observed. Histology showed high cellularity, moderate nuclear atypia, and small rosette formation but neither bizarre tumor cells nor necrosis was present. Mitotic counts were very low (less than 1 per 10 high-power fields) and the MIB-1 labeling index was relatively high (10.1%). Tumor cells were immunohistochemically positive for neural markers such as synaptophysin, neurospecific enolase but not for glial fibrillary acidic protein or S-100. In some parts, cells were strongly reactive for neurofilament protein. Taken together, we made a final diagnosis of PPTID. This is the first presentation of cytological analysis by squash preparation that gives an important clue to accurate diagnosis of pineal parenchymal tumor and to understand its malignant potential. Diagn. Cytopathol. 2008;36:749,753. © 2008 Wiley-Liss, Inc. [source] Differences and relationships of thymidine phosphorylase expression in tumor-associated macrophages and cancer cells in squamous cell carcinoma of the esophagusDISEASES OF THE ESOPHAGUS, Issue 1 2002N. Koide SUMMARY. Thymidine phosphorylase (TP), which has been shown to be identical to platelet-derived endothelial cell growth factor, is expressed in tumor-associated macrophages (TAMs) as well as cancer cells. The aim of this study was to clarify the differences or relationships of TP expression in TAMs and cancer cells in esophageal squamous cell carcinoma (SCC). Tissues samples were taken from 56 patients with esophageal SCC after curative surgery. The expression of TP in TAMs or SCC cells was examined using a monoclonal antibody to TP (clone 654,1). Microvessels in SCC that stained positively for Factor VIII-related antigen were counted (microvessel density, MVD). Macrophages in SCC that stained positively for CD68 antigen were counted (monocytic count). Ki-67 antigen was immunostained with MIB-1, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling was performed, and Ki-67 labeling index (LI) and apoptotic index were calculated. The expression of TP in stromal cells and cancer cells was observed in 43 (76.8%) and 33 patients (58.9%), respectively. There were significant correlations between TP expression in stromal cells (TAMs) as well as in cancer cells and venous invasion, distant metastasis, or MVD. There was a correlation between TP expression in cancer cells and lymph node metastasis, and there were correlations between TP expression in TAMs and monocytic count or Ki-67 LI; however, there was no correlation between TP expression in TAMs and lymph node metastasis. On the other hand, in SCCs with TP expression in both TAMs and cancer cells, higher frequencies of venous invasion and distant metastasis, higher MVD and lower apoptotic index were observed than in other SCCs. The 5-year survival rate in patients with TP expression in both TAMs and cancer cells was poorer than that in patients with TP expression in neither TAMs and cancer cell. In conclusion, these results suggest that co-expression of TP in TAMs and cancer cells is strongly associated with angiogenic promotion and distant metastasis. However, other effects of TP, such as promotion of tumor growth and lymph node metastasis, may be different depending on whether these are expressed in TAMs or cancer cells in esophageal SCCs. Patients with coexpression of TP in TAMs and cancer cells may be associated with a poor prognosis. [source] Expression of DNA repair gene Ku80 in lymphoid neoplasmEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2005Tsai-Yun Chen Abstract:,Objectives:,Ku, a heterodimer of KU70 and Ku80 that binds to double-strand DNA breaks (DSBs) and activates the catalytic subunit (DNA-PKcs) when DNA is bound, is essential in DSB repair and V(D)J recombination. Ku80 is a putative tumor suppressor gene that might play an important role in drug resistance. Our aim was to determine the role of Ku80 in lymphoid malignancy. Patients and methods:,Competitive reverse transcription-polymerase chain reaction assays were performed and the expression levels of Ku80 were measured in normal peripheral blood mononuclear cells (n = 9) and malignant cells from 25 patients with acute lymphoblastic leukemia (ALL) (14 children, 11 adults), and chronic lymphoproliferative disorders (n = 6). The Ku80 transcripts were sequencing for the possibility of mutation. Results:,No mutation or Ku80 variant at the RNA level was seen in any patient samples or in the Raji or CCRF-CEM cell lines. In Ku80 expression, 8.8-, 1.9-, and 6.2-fold mean increases were seen in adult, pediatric ALL, and chronic lymphoid malignancies compared with the control. The Ku80 was significantly higher in adult than in pediatric ALL (P = 0.02). The amount of Ku80 expression in ALL was moderately correlated with peripheral white blood cell counts, but not with Ki67 labeling index. High Ku80 expressers (higher than the mean of all patients with ALL) tended to respond poorly to therapy: Only 22% of high Ku80 expressers achieved durable complete remission compared to 62% of low expressers. Conclusions:,Our study suggests that Ku80 might contribute to generally poor prognoses in adult ALL. [source] Impact of Helicobacter pylori Eradication Therapy on Histologic Change in the Distal EsophagusHELICOBACTER, Issue 4 2006Masanori Toyoda Abstract Background:, Although cases of reflux esophagitis (RE) developing after treatment to eradicate Helicobacter pylori have been discussed in some detail, no reports are available concerning the histologic examination of RE both before and after eradication therapy. Materials and methods:, Sixty-one patients and 111 specimens were investigated using endoscopic and histologic techniques. The histologic findings including basal zone height, papillar height, Ki-67 labeling index, and COX-2 expression before and after treatment for H. pylori infection were compared with those in normal controls and patients with endoscopic RE. Results:, Twelve months after eradication therapy, the incidence of newly developed endoscopic RE was 20% (5/25). Basal zone height and papillar height had increased at 1 month, but had returned to pretreatment levels after 12 months of eradication therapy. The Ki-67 labeling index was significantly increased 1 and 12 months after eradication therapy compared to values before treatment. COX-2 expression gradually increased after the treatment. The phenomena linked to esophagitis appeared after eradication therapy. However, the severity and extent of these signs were not so high after the treatment of H. pylori than those in patients with overt reflux esophagitis. Focusing on the patients with hiatal hernia, papillar height and Ki-67 labeling index increased significantly after eradication therapy, values being almost the same as those in the patients with endoscopic RE. Conclusions:, Hiatal hernia plays an important role in the possible occurrence of hidden RE after treatment for a H. pylori infection. [source] Immunohistologic study on the expressions of ,-fetoprotein and protein induced by vitamin K absence or antagonist II in surgically resected small hepatocellular carcinomaHEPATOLOGY, Issue 6 2001Miwako Fujioka Sixty-eight cases of single hepatocellular carcinoma (HCC) with less than 3 cm of diameter were immunohistochemically examined for the expressions of ,-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II). In cancerous tissues, the expression rate was significantly higher for PIVKA-II (34 cases [50%]) than AFP (21 cases [31%]) (P < .05), suggesting a higher specificity of PIVKA-II to small HCC. Sixteen of the 68 cases (24%) were positive to both AFP and PIVKA-II, and in 8 of the 16 cases, AFP and PIVKA-II expressing areas within a nodule were clearly divided by a fibrous septum. According to histologic grades, PIVKA-II expression was confirmed in 2 of the 15 well-differentiated HCCs, and in the well-differentiated component of 6 of the 12 "nodule-in-nodule",type well-differentiated HCCs. AFP expression was not found in well-differentiated HCCs, but found in 16 of the 40 moderately differentiated HCCs (40%) and in the moderately differentiated component of 3 of the 12 "nodule-in-nodule",type well-differentiated HCCs. The positive rate in the tissues was correlated to the serum levels for both AFP and PIVKA-II. In addition, frequency of tissue,PIVKA-II expression was higher than tissue-AFP expression in the cases whose serum protein level was within the normal range. This indicates that AFP and PIVKA-II have different patterns of tissue expression and of secretion to the blood. In comparison with tissue-AFP,negative cases, tissue-AFP,positive HCCs had a larger tumor size, higher frequencies of portal vein invasion and intrahepatic metastasis, a high Ki-67 labeling index, and a lower rate of recurrence-free survival. Thus, tissue-AFP,positive HCCs are suggested to be biologically more malignant than those HCCs that are AFP-negative and PIVKA-II,positive. [source] The Impact of Interferon Gamma Receptor Expression on the Mechanism of Escape From Host Immune Surveillance in Hepatocellular CarcinomaHEPATOLOGY, Issue 3 2000Mitsuo Nagao M.D. Interferon gamma (IFN-,) plays an important role in host defense mechanism and participates in the progression of chronic liver disease. IFN-, exerts its pleiotrophic effects by transcriptional regulation of expression of numerous genes, such as major histocompatibility complex (MHC) class I and Fas, through interaction with IFN-, receptor (IFN-,-R). Although hepatocytes in normal liver express weak or no IFN-,-R, those in acute and chronic liver disease up-regulate its expression. A study using IFN-,-R ,-chain knock-out mice revealed the actions of IFN-, on tumor cells as an extrinsic tumor-suppressor mechanism. However, it is unclear whether or how hepatocellular carcinoma (HCC) blocks the signal transduction of IFN-, to evade host immune surveillance. We examined the expression of IFN-,-R and IFN-,,inducible genes in 44 cases with HCC using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. In noncancerous liver tissues (n = 38), IFN-,-R expression on the cell surface was up-regulated in 27 cases. In IFN-,-R,negative cases (n = 15), tumor size was larger (P = .032), serum ,-fetoprotein (AFP) level was higher (P = .001), intrahepatic and extrahepatic metastasis was more common (P = .044 and .013, respectively), and Ki-67 labeling index (LI) was higher (P = .041), compared with IFN-,-R,positive cases. Accordingly, the evasion mechanism may play an important role in progression, especially metastasis, in HCC. The significant correlation between the status of IFN-,-R and the expression of Fas and MHC implies that the loss of IFN-,-R might contribute to the mechanism of escape from host immune rejection in HCC. [source] Mesenchymal stem cells enhance growth and metastasis of colon cancerINTERNATIONAL JOURNAL OF CANCER, Issue 10 2010Kei Shinagawa Abstract Recently, mesenchymal stem cells (MSCs) were reported to migrate to tumor stroma as well as injured tissue. We examined the role of human MSCs in tumor stroma using an orthotopic nude mice model of KM12SM colon cancer. In in vivo experiments, systemically injected MSCs migrated to the stroma of orthotopic colon tumors and metastatic liver tumors. Orthotopic transplantation of KM12SM cells mixed with MSCs resulted in greater tumor weight than did transplantation of KM12SM cells alone. The survival rate was significantly lower in the mixed-cell group, and liver metastasis was seen only in this group. Moreover, tumors resulting from transplantation of mixed cells had a significantly higher proliferating cell nuclear antigen labeling index, significantly greater microvessel area and significantly lower apoptotic index. Splenic injection of KM12SM cells mixed with MSCs, in comparison to splenic injection of KM12SM cells alone, resulted in a significantly greater number of liver metastases. MSCs incorporated into the stroma of primary and metastatic tumors expressed ,-smooth muscle actin and platelet-derived growth factor receptor-, as carcinoma-associated fibroblast (CAF) markers. In in vitro experiments, KM12SM cells recruited MSCs, and MSCs stimulated migration and invasion of tumor cells through the release of soluble factors. Collectively, MSCs migrate and differentiate into CAFs in tumor stroma, and they promote growth and metastasis of colon cancer by enhancing angiogenesis, migration and invasion and by inhibiting apoptosis of tumor cells. [source] Selective cyclooxygenase-2 inhibitor downregulates the paracrine epithelial,mesenchymal interactions of growth in scirrhous gastric carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 3 2007Masakazu Yashiro Abstract The importance of cancer-mesenchymal interactions in the aggressive behavior of scirrhous gastric cancer is supported by experimental and clinical evidences. We have previously reported that gastric fibroblasts secretion of keratinocyte growth factor (KGF) underline the remarkable proliferation of scirrhous gastric cancer cells. Cyclooxygenase-2 (COX-2) is not only expressed in cancer cells, but also in interstitial fibroblasts in gastric carcinoma. To clarify the mechanisms responsible for the antiproliferation effect of COX-2 inhibitors, effect of COX-2 inhibitor on the paracrine epithelial,mesenchymal interactions of growth was examined. Scirrhous gastric cancer cell line, OCUM-2M, gastric fibroblasts, NF-21, and COX-2 inhibitor, JTE-522, were used. Growth-interaction was examined by calculating the number of cancer cells or by measuring [3H] thymidine incorporation of cancer cells. Effect of JTE-522 on KGF expression from NF-21 cells and OCUM-2M cells was analyzed by ELISA and RT-PCR. The conditioned medium from gastric fibroblasts significantly stimulated the growth of scirrhous gastric cancer cells. JTE-522 at the concentrations of 10,5 and 10,6 M significantly decreased the growth-stimulating activity of gastric fibroblasts. JTE-522 reduced the expression of KGF mRNA and the production of KGF from gastric fibroblasts. Oral administration of JTE-522 significantly decreased the size of xenografted tumor coinoculated with OCUM-2M cells and NF-21 cells in nude mice. JTE-522 decreased COX-2 expression and Ki67 labeling index within the coinoculated tumor. These findings suggested that a selective COX-2 inhibitor, JTE-522, downregulates KGF production from gastric fibroblasts, resulting in the inhibition of paracrine epithelial,mesenchymal interactions of proliferation between scirrhous gastric cancer cells and gastric fibroblasts. © 2006 Wiley-Liss, Inc. [source] BRAF mutation associated with dysregulation of apoptosis in human colorectal neoplasmsINTERNATIONAL JOURNAL OF CANCER, Issue 6 2005Nobunao Ikehara Abstract To understand the role of BRAF dysfunction in the carcinogenesis and progression/development of colorectal tumors, the authors investigated genetic alterations in the BRAF gene in human colorectal neoplasms as well as the effects of an RAS inhibitor in BRAF -mutant cells. Seven colon cancer cell lines and 116 colorectal tumors (34 adenomas and 82 adenocarcinomas) were analyzed. Genetic alterations in the BRAF and K- ras genes were examined using polymerase chain reaction-single strand conformation polymorphism and direct sequencing analyses. The growth-inhibitory and apoptosis-inducing effects of the FTI-277 RAS inhibitor in colon cancer cell lines were analyzed as well. An immunohistochemical study was also performed to investigate the correlations between the clinicopathologic parameters involved in the Ki-67 labeling index and the number of apoptotic bodies in tumor cells. FTI-277 did not suppress the proliferation of BRAF -mutant cells (WiDr and TCO), but remarkably inhibited the growth of K- ras mutant cells (LoVo). Interestingly, LoVo cells underwent apoptosis by FTI-277 in a dose-dependent manner, whereas WiDr cells were resistant to this agent. In tumor samples, BRAF mutations were found in 1 (3.0%) of 33 adenomas and 6 (7.2%) of 83 adenocarcinomas. No tumor exhibited mutations in both the BRAF and K- ras genes. Neither BRAF nor K- ras mutations correlated with the Ki-67 labeling index immunohistochemically. However, the number of apoptotic bodies was significantly decreased in the BRAF -mutant tumors. Mutation in the BRAF gene may contribute to colorectal carcinogenesis by upregulating the antiapoptotic role of the RAS/RAF/MEK/ERK pathway. © 2005 Wiley-Liss, Inc. [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 ureterINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2005SHUICHI 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] Clear cell myoepithelial carcinoma of the skin.JOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2009A case report Myoepitheliomas are tumors of myoepithelial cells, most frequently diagnosed in the salivary glands. Cutaneous location is very rare, especially for malignant variant. We report a case of recurrent cutaneous myoepithelial carcinoma of the femoral region in a 51-year-old woman. Histologically, the tumor was confined to the dermis and superficial subcutaneous fat tissue, exhibiting typical multinodular pattern. The majority of tumor cells were of clear cell type, although rare epithelioid and spindle cells were also present. Nuclear atypia, mitotic activity of 12 mitoses per 10 microscopic high power fields and Ki-67 labeling index of 20%, as well as three recurrences, corroborated the malignant nature of the tumor. Immunohistochemistry showed positivity for cytokeratin, epithelial membrane antigen, vimentin, S-100 protein and myogenic markers (,-smooth muscle actin and muscle-specific actin HHF-35) in keeping with the myoepithelial cell immunophenotype. Staining for CD34, desmin and HMB-45 was negative. Myoepithelial carcinoma should be considered in the differential diagnosis of cutaneous neoplasms composed predominantly of clear cells. [source] Skp2 and p27kip1 expression in melanocytic nevi and melanoma: an inverse relationship,JOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2004Qing Li Background:, S-phase kinase associated protein-2 (Skp2) ubiquitin ligase p45SKP2 is important in the degradation of p27kip1 (a cyclin dependent kinase inhibitor) and progression through the G1-S cell-cycle checkpoint. Low levels of p27 and high levels of Skp2 are related to poor prognosis in some cancers. Methods:, Clinicopathologic features and immunohistochemical expression of Skp2 and p27kip1 were investigated in 198 melanocytic proliferations: 21 melanocytic nevi, 23 melanoma in situ, 119 primary melanoma, and 35 metastatic melanoma samples. Comparative and survival analyses were performed. Results:, Progressive and significant increases and decreases in the nuclear expression of Skp2 and p27kip1, respectively, was identified moving from melanocytic nevi (0.05 ± 0.2/85 ± 15) to melanoma in situ (3 ± 2/45 ± 20) to primary cutaneous melanoma (12 ± 9/30 ± 25) to metastatic melanoma (25 ± 15/15 ± 20) (p , 0.006). Expression of these proteins also significantly correlated with increasing American Joint Committee on Cancer (AJCC) T (tumor) classification and AJCC stage (p , 0.01). Moreover, the level of these two proteins exhibited a significant inverse relationship (r = ,0.4, p = 0.0001). Skp2 cytoplasmic labeling index of >20% predicted worse 10-year overall survival (38% vs. 86%, p = 0.04) in primary melanoma. Neither p27 nor Skp2 nuclear expression impacted significantly on prognosis. Conclusions:, Gain of Skp2 and loss of p27kip1 protein expression are implicated in melanoma progression where the level of p27kip1 may be regulated by targeted proteolysis via Skp2. Cytoplasmic expression of Skp2 defines a subset of aggressive melanomas and could represent another pathway of deregulation of the cell cycle. [source] Role of cyclooxygenase-2 and inducible nitric oxide synthase in pancreatic cancerJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2002Gu Kong Abstract Background and Aim: Recently, it has been recognized that both cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) produce important endogenous factors of human tumor progression. However, the clinicopathological and biological significance of the expression of COX-2 and iNOS in pancreatic cancer remains unclear. The objective of this study is to find the possible roles and clinical significance of COX-2 and iNOS expression in pancreatic cancer. Methods: Seventy-two pancreatic adenocarcinoma tissue specimens were obtained through surgical resection. We investigated the immunohistochemical expression of COX-2 and iNOS in respect to variable clinicopathological characteristics, proliferation activity (by Ki-67 expression), apoptosis (by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling stain), and microvessel density (by CD34 expression; angiogenesis). Results: Immunohistochemical investigations demonstrated immunolabeling of tumor cells with the primary antibodies, bovine anti-iNOS and anti-COX-2 antibodies. The COX-2 and iNOS positive rates were 41.7 and 66.7%, respectively. There was significant correlation between positive COX-2 and positive iNOS expression (P = 0.043). The proliferation index (Ki-67 labeling index) was higher in COX-2 positive specimens compared to COX-2 negative specimen (P = 0.015). The apoptotic index of positive iNOS expressions was significantly higher than negative expressions (P < 0.001). The expression of COX-2 and iNOS proteins did not correlate with age, sex, serum bilirubin, CA-19,9, location, size, American Joint Committee on Cancer stage, differentiation, distant metastasis, patient survival, or microvessel density. Conclusions: Although the pattern of positive expression was similar in both enzymes, the effect on tumor progression differed; iNOS expression may play a role in apoptosis of tumor cell, while COX-2 expression may contribute to tumor proliferation. However, COX-2 and iNOS expression is not related to prognosis in patients with pancreatic cancer. © 2002 Blackwell Publishing Asia Pty Ltd [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 dysplasiaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2003Hideo 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] Histopathological and immunohistochemical analysis of calcifying odontogenic cystsJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 10 2001Mitsuhide Yoshida Abstract: Method and Results: Calcifying odontogenic cysts (COCs) were examined histopathologically and immunohistochemically to characterize the histological and cytological properties of these lesions. Histopathologically, COCs showed thin or thick lining epithelium with ghost cells. COCs were classified according to proliferative type or nonproliferative type lining epithelium, the presence or absence of ameloblastomatous appearance, and the presence or absence of odontoma in the cyst walls. Immunohistochemically, amelogenin protein was expressed chiefly in ghost cells, whereas cytokeratin 19 (CK19) and bcl-2 proteins were expressed chiefly in lining epithelial cells. The proportion of cases positive for bcl-2 protein was slightly higher in COCs with odontoma than in those without odontoma. Lining epithelial cells sporadically showed positive reactions for Ki-67 antigen. Mean Ki-67 labeling index was slightly greater in COCs with proliferative type lining epithelium, COCs with ameloblastomatous appearance of the cyst walls, and COCs with odontoma of the cyst walls than in COCs without these histological features. Our results suggest that ghost cells or lining epithelial cells show ameloblastic cytodifferentiation or odontogenic epithelial characteristics, that bcl-2 protein is associated with survival of lining epithelial cells in COCs, and that high proliferation potential is associated with ameloblastomatous proliferation or combined odontoma. COCs exhibited various histological features with several transitional forms, and immunohistochemical examinations revealed little or no difference in cytodifferentiation and cellular activity among COCs. Conclusion: We conclude that COCs with various histological features have neoplastic potential and may not be separate entities within the same histological spectrum. [source] Liver transplantation for non,hepatocellular carcinoma malignancy: Indications, limitations, and analysis of the current literatureLIVER TRANSPLANTATION, Issue 8 2010Eric J. Grossman Orthotopic liver transplantation (OLT) is currently incorporated into the treatment regimens for specific nonhepatocellular malignancies. For patients suffering from early-stage, unresectable hilar cholangiocarcinoma (CCA), OLT preceded by neoadjuvant radiotherapy has the potential to readily achieve a tumor-free margin, accomplish a radical resection, and treat underlying primary sclerosing cholangitis when present. In highly selected stage I and II patients with CCA, the 5-year survival rate is 80%. As additional data are accrued, OLT with neoadjuvant chemoradiation may become a viable alternative to resection for patients with localized, node-negative hilar CCA. Hepatic involvement from neuroendocrine tumors can be treated with OLT when metastases are unresectable or for palliation of medically uncontrollable symptoms. Five-year survival rates as high as 90% have been reported, and the Ki67 labeling index can be used to predict outcomes after OLT. Hepatic epithelioid hemangioendothelioma is a rare tumor of vascular origin. The data from single-institution series are limited, but compiled reviews have reported 1- and 10-year survival rates of 96% and 72%, respectively. Hepatoblastoma is the most common primary hepatic malignancy in children. There exist subtle differences in the timing of chemotherapy between US and European centers; however, the long-term survival rate after transplantation ranges from 66% to 77%. Fibrolamellar hepatocellular carcinoma is a distinct liver malignancy best treated by surgical resection. However, there is an increasing amount of data supporting OLT when resection is contraindicated. In the treatment of either primary or metastatic hepatic sarcomas, unacceptable survival and recurrence rates currently prohibit the use of OLT. Liver Transpl 16:930-942, 2010. © 2010 AASLD. [source] Overexpression of cyclin D2 is associated with increased in vivo invasiveness of human squamous carcinoma cellsMOLECULAR CARCINOGENESIS, Issue 3 2002Shao Chen Liu Abstract Overexpression of cyclin D2 was studied in 10 human squamous cell carcinoma lines, to establish whether this gene plays a role in tumor progression. We found that those cell lines that overexpressed cyclin D2 (CCND2) had the most invasive in vivo behavior. The invasive ability of the cell lines was determined by evaluating the penetration of carcinoma cells into the tracheal wall in an in vivo assay with de-epithelialized tracheas transplanted into the subcutaneous tissue of nude mice. From five cell lines that exhibited low invasive ability, we selected two that had very little CCND2 expression (SCC9 and SCC15), to evaluate whether CCND2 gene transfer would increase the invasive behavior. After confirming the successful transfer of CCND2 by Northern, Western, and kinase-activity assays, we assessed the in vivo invasive behavior of the CCND2 -transfected cells and their respective vector alone,transfected controls. The cell lines containing the transferred CCND2 gene had a significantly higher invasive ability than respective controls. This was accompanied by a moderate increase in gelatinase activity. In addition, the in vitro proliferative abilities, under normal culture conditions, of the parental CCND2 - transfected and vector alone,transfected cells were found to be similar, as was the in vivo labeling index of Ki-67 in the tracheal transplants. These results indicated that the overexpression of CCND2 in squamous cell carcinoma lines modulates cell proliferation after induced quiescence and also has a powerful enhancing effect on in vivo aggressive growth behavior. © 2002 Wiley-Liss, Inc. [source] Benign myoepithelioma of the breast: Origin and developmentPATHOLOGY INTERNATIONAL, Issue 6 2009Hajime Hikino A case of benign myoepithelioma of the breast in a 55-year-old woman is described. The tumor was a well-circumscribed solid mass, measuring 13 × 12 mm. Histopathology indicated that the tumor was composed of entirely myoepithelial cells, which was confirmed by immunoreactivity to calponin and S-100. There was no ductal differentiation in the tumor, and staining for pan-cytokeratin and epithelial membrane antigen was weak and negative, respectively. Although the biological behavior of the tumor remains to be ascertained, the tumor was considered to be myoepithelioma with benign features due to mild nuclear pleomorphism, sparse mitotic figures, low Ki-67 labeling index and low S-phase fraction. Diagnostic confusion between benign myoepithelioma and other myoepithelial-rich cell tumors is possible. Considering the classification of myoepithelial tumor in the salivary glands, benign myoepithelioma of the breast may possess a different development process from adenomyoepithelioma. [source] L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancerPATHOLOGY INTERNATIONAL, Issue 1 2009Takeshi Sakata To find reliable biomarkers for high-grade malignancy, the relationship between immunohistochemical L-type amino-acid transporter 1 (LAT1) expression of biopsy samples, determined with the newly developed monoclonal antibody against human LAT1, and prognosis of patients with prostate cancer, was investigated. The intensity and score of immunohistochemical LAT1 expression of first biopsy samples were assessed using the modified Sinicrope et al. method and were found to be correlated with poor survival for the study group of 114 surgically treated patients as a whole (P = 0.0002 and 0.0270, respectively). LAT1 intensity further had a significant relationship (P = 0.0057) with prognosis in pathological T3 + T4 groups. Multivariate analysis indicated that the LAT1 intensity and score were more reliable prognostic markers, compared with the Gleason score and the Ki-67 labeling index. A relationship of the LAT1 intensity and score with prognosis could also be confirmed in 63 patients with inoperable cancer (P = 0.0070 and <0.0001, respectively). Similarly, significant differences in prognosis were confirmed in clinical T3 + T4 groups (P = 0.0091 and 0.0244, respectively). Moreover, the combination of LAT1 expression and Gleason score was found to have a more reliable correlation with prognosis. Thus, elevated LAT1 expression in prostate cancers is a novel independent biomarker of high-grade malignancy, which can be utilized together with the Gleason score, which is mainly dependent on cellular and structural atypia, to assess prognosis. [source] Immunohistochemical study of the relationship between Ki-67 labeling index of proliferating cells of gynecomastia, histological phase and duration of diseasePATHOLOGY INTERNATIONAL, Issue 11 2006Seishi Kono Gynecomastia is a benign proliferative lesion caused by various etiological factors and may result from a relative imbalance between serum estrogen and androgen levels. The histological alterations are similar, and gynecomastia can progress from a florid type to a fibrous type. The Ki-67 labeling index (LI) of gynecomastia specimen was investigated and higher Ki-67 LI was observed in florid and intermediate than in fibrous gynecomastia (P = 0.017). A correlation was found between the duration of disease and Ki-67 LI (P = 0.041): the shorter the duration the higher the Ki-67 LI. Thus, Ki-67 LI seems a useful tool to examine proliferation activity of gynecomastia and can assist in determination of appropriate treatment of gynecomastia with hormonal therapy. [source] Uterine lipoleiomyoma: A histopathological review of 17 casesPATHOLOGY INTERNATIONAL, Issue 10 2004Thida Aung Lipoleiomyoma is a rare uterine tumor. The exact frequency and proliferation activity are not yet known. This study aims to know the frequency and evaluate the relation with renal angiomyolipoma. Lipoleiomyoma cases were immunohistochemically stained by antibodies for Ki-67, melanoma specific antigen HMB45, S-100 protein, and , smooth muscle actin (,-SMA). Frequency of uterine lipoleiomyoma among ,uterine ,myomatous ,tumor ,was ,17/4904 ,(0.35%) ,in the Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School database (1983,2003). Patients ranged from 45 to 74 years of age, and 10 cases were associated with leiomyoma. Six of 17 (35%) cases showed areas with renal angiomyolipoma-like vessels and atypical cellular features. Immunostaining was available in 12 cases. By Ki-67 labeling index, both muscle (average 1.38%) and fat (average 1.17%) portions of the tumor had greater proliferation than normal myometrium (average 0.76%), which suggests that fat portions of the tumor are proliferating adipose tissue rather than fatty degeneration of muscular counterpart. HMB45 antigen, which is positive in renal angiomyolipoma, was negative in three uterine cases having angiomyolipoma-like vessels (3/12). However, HMB45 antigen was positive in spindle-shaped tumor cells of three cases (3/12) which lacked angiomyolipoma-like vessels. Presence of angiomyolipoma-like blood vessels in these tumors is not an uncommon feature. However, the diagnosis of uterine angiomyolipoma should not be based on the result of HMB45 antigen immunoreactivity alone. [source] Differentiation, proliferation and retinoid receptor status of papillary carcinoma of the thyroidPATHOLOGY INTERNATIONAL, Issue 4 2003Weihua Tang Messenger RNA expression of retinoic acid receptors (RAR,, RAR, and RAR,) and retinoid X receptors (RXR,, RXR, and RXR,) was examined using reverse transcription-polymerase chain reaction in 42 papillary thyroid carcinomas (PTCs). A loss of mRNA expression was observed in 18 cases of the 42 PTCs, including three cases for RAR,, 14 cases for RAR,, six cases for RXR, and five cases for RXR,. The expressions of RAR, and RXR, were found in all 42 PTCs. Based on Ki 67/MIB1 labeling index (LI), the 42 PTCs were classified into Group A (20 cases; LI = 0,2%), Group B (17 cases; LI = 2,5%) and Group C (5 cases; LI > 5%). The PTCs of groups B and C showed solid, trabecular or scirrhous arrangements, infiltrative growth, loss of cellular polarity and cohesiveness more frequently, but capsulated growth pattern less frequently, when compared with PTCs of Group A. They also showed more frequent extrathyroidal extension than Group A. However, no significant differences were identified in sex, age, nodal status and tumor size. Loss of expression for one or more retinoid receptors frequently occurred in groups B and C. These results suggest that the loss of retinoid receptors might occur during the loss of differentiation and tumor progression of PTC. [source] Quantitative immunohistochemical evaluation of MIB-1 labeling index in adult soft-tissue sarcomas by computer-assisted image analysisPATHOLOGY INTERNATIONAL, Issue 7 2002Tadashi Hasegawa We have found that the MIB-1 grade, based on tumor differentiation/histological type, necrosis and Ki-67 (MIB-1) score, is a valid and reproducible prognostic system for adult soft-tissue sarcomas. However, there are limited data available on Ki-67 labeling indices (LI) from adult soft-tissue sarcomas for testing the validity of quantitative image analysis . In this study, the records of 146 adult patients with soft-tissue sarcomas of the extremities and trunk were retrieved, and MIB-1 immunostaining was carried out for the grading. The counted MIB-1 LI values and the scores estimated from microscopic observation were defined as the gold standard. The correlation between MIB-1 LI as assessed by computer-assisted image analysis and by microscopic observation was determined. The image analysis -based MIB-1 LI was highly correlated with the microscopic observation-based MIB-1 LI (r = 0.87, 95% confidence interval (CI) = 0.82,0.92). In addition, agreement between the MIB-1 scores was very high (kappa statistic = 0.83, 95% CI = 0.75,0.91), as was the percentage agreement (89%, 95% CI = 82.8,93.6%) between the results from image analysis and microscopic observation. We conclude that quantitative immunohistochemical evaluation of MIB-1 LI by image analysis enables pathologists to improve interobserver agreement in the assessment of MIB-1 score, and can help to objectively assign the correct histological grade to cases of adult soft-tissue sarcoma, resulting in optimal clinical management. [source] Malignant peripheral nerve sheath tumor arising in benign ancient schwannoma: A case report with an immunohistochemical studyPATHOLOGY INTERNATIONAL, Issue 2 2000Yoshiki Mikami A rare example of malignant transformation in an ancient schwannoma arisng in the right side of the neck of a 51-year-old man without any clinical manifestations suggesting neurofibromatosis is described. The tumor, approximately 4 cm at its largest dimension, was well circumscribed and had a direct connection with the sympathetic nerve. Microscopically, the central portion of the tumor showed features of ancient schwannoma characterized by extensive hyalinization with cystic degeneration, scattered spindle cells with hyperchromatic and tapered nuclei, and some symplastic changes. However, predominantly in the outer portion, a proliferation of spindle-shaped cells with enlarged nuclei was present. The nuclei of these cells showed irregular contours, coarse granular chromatin texture, and conspicuous nucleoli. Mitotic figures and small necrotic foci with scattered apoptotic bodies were also seen. Immunohistochemically, S-100 protein was almost negative in areas consisting of overtly atypical cells where the mitotic index evaluated with MIB-1 antibody was 30.5%. In contrast, S-100-positive bland spindle cells were scattered in an extensively hyalinized area with a labeling index less than 3%. P53 protein was strongly positive in atypical spindle cells. Although it is a very uncommon event, definite nuclear atypia, frequent mitotic figures, and the existence of small necrotic foci should be recognized as indicating a diagnosis of malignant degeneration of benign schwannoma. Immunohistochemistry would be useful as an ancillary technique in such a setting. [source] Minoxidil, a KATP channel opener, accelerates DNA synthesis following partial hepatectomy in ratsBIOFACTORS, Issue 1 2005Keiichi Yamasaki Abstract A large number of studies have reported the action of KATP channel openers in accelerating the proliferation of hepatocytes and many other cell types in vitro. Few studies, however, have examined the proliferative effect of KATP channel openers in vivo. The aim of this study was to determine whether the KATP channel opener minoxidil accelerates liver regeneration after partial hepatectomy (PH) in vivo. Male Wistar rats underwent a 70% partial hepatectomy (PH) after receiving a subcutaneous injection of minoxidil (0.01 mg/kg or 0.03 mg/kg). Some of the rats were intravenously treated with 5-hydroxydecanoic acid (5-HD, 10 mg/kg) just before the minoxidil injection. Seventy-two hours after PH, DNA synthesis was immunohistochemically assessed by bromodeoxyuridine (BrdU) incorporation into the nuclei. Minoxidil induced significant and dose-dependent increase in the BrdU labeling index after PH, and 5-HD reversed this minoxidil-induced change. Minoxidil did not significantly affect the changes in liver weight and liver function after PH. The hepatic levels of prealbumin decreased by about 60% after PH and minoxidil inhibited the decrease. In conclusion, the KATP channel opener minoxidil enhanced DNA synthesis after PH without affecting the liver function. [source] Teratogenic effects of bis-diamine on the developing myocardiumBIRTH DEFECTS RESEARCH, Issue 3 2004Nobuhiko Okamoto Abstract BACKGROUND Bis-diamine induces conotruncal anomalies and disproportional ventricular development in rat embryos when administered to the mother. To evaluate the mechanisms of disproportional ventricular development in the anomalous heart, we analyzed the morphology of the embryonic heart and investigated cardiomyocytic DNA synthesis and apoptosis. METHODS A single dose of 200 mg of bis-diamine was administered to pregnant rats Wistar on day 9.5 of pregnancy. The embryos were removed on each embryonic day from 10.5 to 18.5. Expression of cardiotrophin-1 and hepatocyte growth factor was investigated on the sections, and cardiotrophin-1, hepatocyte growth factor and myocyte enhancer factor 2 mRNA expression was examined by reverse transcriptase,polymerase chain reaction. Myocardial DNA synthesis was investigated using 5-bromo-2,-deoxyuridine and the labeling index was calculated for each heart. Apoptosis was also analyzed using TUNEL reaction and electrophoresis of DNA fragmentation. RESULTS The embryos treated with bis-diamine had conotruncal anomalies associated with thin left ventricular wall in the later stage. The labeling index on embryonic day 15.5 and 16.5 was significantly lower than those in the controls. Hepatocyte growth factor and cardiotrophin-1 mRNA expression was upregulated on embryonic day 12.5 and 15.5 in bis-diamine,treated hearts. Fewer apoptotic cells were detected in the hearts of bis-diamine,treated embryos than in control hearts from embryonic day 14.5 to 16.5. CONCLUSIONS The ventricular disproportion in the bis-diamine,treated heart may be caused by the early myocardial differentiation delay and poor proliferation and reduced apoptosis associated with anomalous circulatory condition in the later stage. Birth Defects Research (Part A), 2004. © 2004 Wiley-Liss, Inc. [source] Vascular Patterns in Glioblastoma Influence Clinical Outcome and Associate with Variable Expression of Angiogenic Proteins: Evidence for Distinct Angiogenic SubtypesBRAIN PATHOLOGY, Issue 2 2003Peter Birner MD No data exist on angiogenic patterns and their prognostic impact in human glioblastoma. Such data are relevant for translation of antiangiogenic therapies into clinical applications. Using immunohistochemistry for CD34, we assessed vascular patterns in 114 primary glioblastomas. Vascular patterns comprised unevenly distributed glomeruloid/garland-like/clustered bizarre vascular formations and evenly distributed delicate capillary-like microvessels ("classic" vascular pattern). The combination of low content of bizarre vascular formations and prominent classic vascular pattern (n=29) was an independent factor for longer survival (p= 0.006, Cox regression), as well as postoperative high Karnofsky performance status (p=0.005). In patients with a prominent classic vascular pattern, there was no difference of MIB1 labeling index whereas microvessel density and apoptotic index (TUNEL) were significantly higher as compared to all other patients (p<0.05). In addition, diffuse expression of hypoxia-inducible factor (HIF)-1, and strong expression of vascular endothelial growth factor were more common (p<0.05, Chi-square test). FISH revealed loss of chromosomes 1p and 19q only in 1/7 long-time survivors with classic pattern. We conclude that vascular patterns in primary glioblastoma influence clinical outcome and associate with variable expression of angiogenic proteins. Our findings denote for the first time distinct angiogenic subtypes of human glioblastoma which may prove relevant for anti-angiogenic therapy approaches. [source] | |||||||||||||||||||||||||||||||