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Malignant Transformation (malignant + transformation)
Selected AbstractsAdenocarcinoma arising from respiratory ciliated epithelium in benign cystic teratoma of the ovary: A case report with analyzes of the CT, MRI, and pathological findingsJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2008Tetsuro Yahata Abstract The malignant transformation of mature cystic teratoma is rare, thus occurring in only 1,2% of all cases. The most common malignancy arising in mature cystic teratoma is squamous cell carcinoma. Adenocarcinoma occurs with less frequency. We herein present a patient with an ovarian mature cystic teratoma who demonstrated a malignant transformation to well-differentiated adenocarcinoma. Malignant transformation was diagnosed preoperatively by contrast enhanced computed tomography (CT) and magnetic resonance imaging (MRI). Microscopically and immunohistochemically, the adenocarcinoma was considered to have arisen from the ciliated respiratory epithelium. After a 28-month of follow-up period, she remains free of the disease. This is the third reported case of adenocarcinoma arising in the respiratory epithelium of an ovarian mature cystic teratoma. Contrast enhanced CT and MRI are useful for making a preoperative diagnosis and an immunohistochemical study is helpful for defining its origin. [source] Mucinous adenocarcinoma and strumal carcinoid tumor arising in one mature cystic teratoma of the ovary with synchronous cervical cancerJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2003Seok Mo Kim Abstract Malignant transformation of mature cystic teratoma is an uncommon complication. While any of the constituent tissues of a teratoma has the potential to undergo malignant transformation, squamous cell carcinoma is the most commonly associated cancer. We present an unusual case of a postmenopausal woman with synchronous mucinous adenocarcinoma and strumal carcinoid tumor from one of two ovarian mature cystic teratomas (one in each ovary) with synchronous cervical cancer. We suggest that malignant transformation of mature cystic teratoma and synchronous cervical cancer be treated by hysterectomy, chemotherapy, and radiotherapy. [source] Malignant transformation of supratentorial clear cell ependymomaNEUROPATHOLOGY, Issue 3 2009Masanori Kurimoto Recurrence of clear cell ependymoma is not a rare condition, but malignant transformation of clear cell ependymoma has not yet been well presented. The authors report a 44-year-old man who presented with progressive right hemiparesis. A brain tumor in the left frontal premotor area was removed and an initial pathological diagnosis of oligodendroglioma was made. The tumor recurred 4 months later, and reoperation of the tumor and adjuvant local radiotherapy were performed. The patient subsequently underwent surgical removal of recurrent tumors on another four occasions (6 times in total) during a period of 11 years and finally died of the original disease. Histopathological studies of all surgical and autopsy specimens were carried out. The first and second surgical specimens did not contain any ependymal rosettes or pseudorosettes, and thus a diagnosis of oligodendroglioma was made. However, the third surgical specimen showed pseudorosettes. At this time, the tumor had an ultrastructural appearance compatible with ependymoma. Thereafter, the recurrent tumors showed anaplastic features such as nuclear pleomorphisms and necrosis with pseudopallisading. The autopsy specimens resembled a feature of glioblastoma but the tumor was sharply demarcated from the surrounding parenchyma. [source] Malignant transformation of mature cystic teratoma to squamous cell carcinoma involves altered expression of p53- and p16/Rb-dependent cell cycle regulator proteinsPATHOLOGY INTERNATIONAL, Issue 12 2008Atsuko Iwasa Ovarian mature cystic teratomas (MCT) uncommonly undergo malignant transformation to squamous cell carcinoma (SCC). While alterations in the p53 tumor suppressor gene and protein have been shown, few studies have analyzed other molecular changes leading to this malignant conversion. The purpose of the present study was to investigate 21 samples of SCC arising in MCT for altered expression in known p53- and p16/Rb-dependent cell cycle regulatory proteins, and the association between their expression and cellular proliferation and histological features. Overexpression of the p53 protein was observed in 14 SCC (67%), while four (19%) had point mutations in the p53 gene. Reduced expression of the p16 protein was observed in 18 SCC (86%), while p16 gene alterations (hypermethylation (29%) and point mutation (33%)) were found in 11 (52%). Furthermore, a statistically significant correlation was observed between p53 and Rb overexpression (P = 0.0010), and the overexpression of both p53 and Rb was respectively significantly correlated with increased cellular proliferation. The results indicate that alterations in both the p53 and p16-Rb pathways are associated with SCC arising in MCT. [source] Malignant transformation of atypical endometrial hyperplasia after progesterone therapy showing germ-cell tumor-like differentiationPATHOLOGY INTERNATIONAL, Issue 6 2004Masanori Yasuda A 31-year-old woman was treated for atypical endometrial hyperplasia (AEH) with high-dose medroxyprogesterone acetate (MPA) therapy to preserve fertility. The AEH was found by repeated cytologic and histologic examinations to have completely disappeared with the therapy, but 3 years after her last follow up she required emergency surgery to treat severe genital bleeding. The hysterectomied uterus consisted mostly of poorly differentiated adenocarcinoma, G3 endometrioid type. Minor AEH was present in the exophytic area, in which some glands were cystically dilated. Part of the AEH had transformed into other histologic features with germ-cell-like differentiation, demonstrated by immunohistochemical positive reaction of placental alkaline phosphatase, alpha-fetoprotein, and human chorionic gonadotrophin. Recurrent AEH had undergone malignant transformation, resulting in the development of well- and poorly differentiated adenocarcinoma and tumor exhibiting germ-cell-like differentiation. The patient died of a massive tumor extension 7 months after surgery. The AEH before MPA therapy and the recurrent tumors had genetically different characteristics based on evidence of a loss of heterozygosity, detected at D8S1132 (chromosomal locus, 8q22.1) in the latter but not in the former, by analysis of genetic alterations using microsatellite markers. [source] Management of Nevus Sebaceous and the Risk of Basal Cell Carcinoma: An 18-Year ReviewPEDIATRIC DERMATOLOGY, Issue 6 2009Heather Rosen M.D., M.P.H. It may undergo malignant transformation to basal cell carcinoma (BCC). However the incidence and lifetime risk of malignant transformation is unknown. We performed an 18-year review of all NS excisions at our institution, to report the number of cases of BCC and other neoplasms within excised NS. The aim is to inform physicians who must weigh the risks in recommending excision of a NS in a pediatric patient population with the risk of malignancy. After a database query for years 1990,2008, charts were reviewed and data were extracted on demographics and surgical history relating to NS. Thirty-one NS with abnormal findings were reviewed microscopically by a dermatopathologist. There were 651 NS distinct lesions among 631 patients and 690 excisions. Twenty-one intralesional diagnoses were found in 18 patients. Five patients (0.8%) had BCC (mean age 12.5 yrs, range 9.7,17.4 yrs). Seven (1.1%) had syringocystadenoma papilliferum (SP) (mean age 8.8 yrs, range 1.7,16.9 yrs), a lesion that may undergo malignant transformation. Malignant transformation of NS can occur in childhood or adolescence. We believe all NS should be excised, however timing of excision can be flexible. Our data do not support age cutoffs or morphologic changes to determine optimal excision time. In conjunction with the treating physician, the parent and patient may weigh the small risk of malignant transformation of NS against the morbidity associated with excision and anesthesia. [source] Cloning and identification of EDD gene from ultraviolet-irradiated HaCaT cellsPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 6 2006Nishma Gupta Ultraviolet (UV) radiation is one of the most important external stimuli that affects skin by inducing cancer, inflammation and cell death. To identify the regulation of genes regulated by UV during transformation, normal human keratinocyte cell line, HaCaT, was exposed to multiple doses of UVA+B (UVA , 150,200 mJ/cm2 and UVB , 15,20 mJ/cm2× 6). Malignant transformation was confirmed by formation of colonies on soft agar and DNA methylation assay. To identify the genes involved in this process, random amplification of polymorphic DNA using RNA from unexposed and multiple exposed cells was performed after each exposure. A few up-regulated genes were identified, cloned and sequenced. One of the genes had homology to EDD (E3 identified by differential display) that was up-regulated at second exposure but was down-regulated in colony-forming cells (cells that received six or more exposures) as determined by RT-PCR. This is a progesterone-induced gene and progesterone treatment reduced the extent of colony formation on soft agar plate. It is possible that hormone therapy may have some effects on skin cancer in vivo. [source] Differential expression of the calcium sensing receptor and combined loss of chromosomes 1q and 11q in parathyroid carcinomaTHE JOURNAL OF PATHOLOGY, Issue 1 2004Carola J Haven Abstract Malignant transformation of parathyroid tumours is rare. Nevertheless, this small subset of malignant tumours often creates diagnostic and therapeutic problems. In this work, the morphological characteristics of 26 primary parathyroid carcinomas and seven metastases have been studied. Furthermore, immunohistochemical expression profiles for the calcium sensing receptor (CASR), cyclin D1 (CCND1), and Ki-67 were determined for parathyroid carcinomas and compared with adenomas and hyperplasias using a tissue microarray. Loss of heterozygosity (LOH) of the chromosome 1q region containing the HRPT2 gene and chromosome 11q (MEN1) was determined in the carcinomas. In contrast to the adenomas and hyperplasias, 31% of carcinomas demonstrated down-regulation of CASR. A significant correlation was found between CASR expression and the Ki-67 proliferation index. Chromosome 1q and chromosome 11q LOH were found in 12 of 22 (55%) and 11 of 22 (50%) carcinomas tested, respectively. Combined 1q and 11q LOH was seen in 8 of 22 (36%) carcinomas, in contrast to the low percentage of LOH reported in both regions in adenomas. In conclusion, this study demonstrates that combined 1q and 11q LOH in parathyroid tumours is suggestive of malignant behaviour. Strong down-regulation of the CASR protein is seen in a proportion of parathyroid carcinomas with a high proliferation index. Copyright © 2004 John Wiley & Sons, Ltd. [source] GOLPH2 and MYO6: Putative prostate cancer markers localized to the Golgi apparatusTHE PROSTATE, Issue 13 2008Shuanzeng Wei Abstract BACKGROUND Malignant transformation is often accompanied by morphological and functional alterations in subcellular organelles. The Golgi apparatus is a subcellular structure primarily involved in modification and sorting of macromolecules for secretion and transport to other cellular destinations. Molecular alterations associated with the Golgi apparatus may take place during prostate carcinogenesis but such alterations have not been documented. METHODS To demonstrate that the Golgi apparatus undergoes alterations during prostate carcinogenesis, we examined the expression and localization of two candidate molecules, Golgi phosphoprotein 2 (GOLPH2) and myosin VI (MYO6), both overexpressed in prostate cancer as initially identified by expression microarray analysis. RESULTS Elevated GOLPH2 expression in prostate cancers was validated through real-time RT-PCR, Western blot, and tissue microarray analysis, and its Golgi localization in surgical prostate cancer tissues confirmed using two-color immunofluorescence. In addition, distinctive juxtanuclear MYO6 staining pattern consistent with Golgi localization was observed in surgical prostate cancer tissues. Two-color immunofluorescence revealed intensive Golgi-specific staining for both GOLPH2 and myosin VI in prostate cancer cells but not in the adjacent normal prostate epithelium. CONCLUSIONS We show that the Golgi apparatus in prostate cancer cells differs from the normal Golgi by elevated levels of two molecules, GOLPH2 and MYO6. These results for the first time demonstrated consistent cancer cell-specific alterations in the molecular composition of the Golgi apparatus. Such alterations can be explored for discovery of novel prostate cancer biomarkers through targeted organellar approaches. Prostate 68: 1387,1395, 2008. © 2008 Wiley-Liss, Inc. [source] Malignant risk and surgical outcomes of presacral tailgut cysts,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 4 2010K. L. Mathis Background: Presacral tailgut cysts are uncommon and few data exist on the outcomes following surgery. Methods: Patients undergoing tailgut cyst resection at the Mayo Clinic between 1985 and 2008 were analysed retrospectively. Demographic data, clinicopathological features, operative details, postoperative complications and recurrence were reviewed. Results: Thirty-one patients were identified (28 women), with a median age of 52 years. Seventeen patients were symptomatic and 28 had a palpable mass on digital rectal examination. Median cyst diameter was 4·4 cm. Four patients had a fistula to the rectum. Complete cyst excision was achieved in all patients; eight underwent distal sacral resection or coccygectomy. Postoperative complications occurred in eight patients but without 30-day mortality. Malignant transformation was present in four patients: adenocarcinoma in three and carcinoid in one. The cyst recurred in one patient after surgery for a benign lesion. Conclusion: Presacral tailgut cysts should be removed due to the risk of malignant transformation. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesisCANCER SCIENCE, Issue 5 2004Reiji Kannagi Malignant transformation is associated with abnormal glycosylation, resulting in the synthesis and expression of altered carbohydrate determinants including sialyl Lewisa and sialyl Lewisx. The sialyl Lewisa and sialyl Lewisx determinants appear in the sera of patients with cancer, and are extensively utilized for serum diagnosis of cancers in Japan. Sialyl Lewisa and sialyl Lewisx are involved in selectin-mediated adhesion of cancer cells to vascular endothelium, and these determinants are thought to be closely associated with hematogenous metastasis of cancers. Recent progress in this area includes the following: 1. Substantial increases in solid clinical statistics that further confirm the contribution of these determinants in the progression of a wide variety of cancers; 2. Elucidation of the ligand specificity of the three family members of selectins and evaluation of the roles of these molecules in cancer cell adhesion; and 3. Advances in the study of the mechanism that leads to the enhanced expression of the sialyl Lewisa/x determinants in malignant cells. These recent results have confirmed that these determinants are not merely markers for cancers, but are functionally implicated in the malignant behavior of cancer cells. The results also suggested that the increase of these determinants in malignant cells is an inevitable consequence of the malignant transformation of cells. Considerable new knowledge has also been accumulated regarding the therapeutic implications for suppression of hematogenous metastasis targeting this cell adhesion system. [source] Quantitative cytological assessment of a persistent oral lesion that underwent malignant transformation: a case reportCYTOPATHOLOGY, Issue 1 2001N. Mollaoglu First page of article [source] Malignant Eccrine Spiradenoma: A Case Report and Review of the LiteratureDERMATOLOGIC SURGERY, Issue 1 2001Masashi Ishikawa MD Background. Eccrine spiradenoma is a well-differentiated benign tumor of the sweat glands. Malignant change arising within eccrine spiradenoma is rare. Objective. We describe a patient with malignant eccrine spiradenoma exhibiting both carcinomatous and sarcomatous differentiation. Methods. Case report and literature review. Results. A 37-year-old woman noted enlargement of a left axillary tumor that had been present for 20 years. The tumor was resected and the specimen, measuring 3.0 cm × 1.5 cm, revealed an encapsulated benign eccrine spiradenoma as well as an undifferentiated carcinoma possessing both carcinomatous and sarcomatous components. A transition zone was evident between the benign eccrine spiradenoma and the undifferentiated carcinoma, suggesting that the latter had arisen from the benign tumor. The malignant areas consisted principally of undifferentiated carcinoma (70%), although squamous cell carcinoma (10%), adenocarcinoma (10%), and chondrosarcomatous (10%) components were also present. Numerous mitotic figures were noted within the areas of malignant change, suggesting that the tumor was aggressive in nature. The patient died of systemic metastases 7 months after diagnosis. Conclusion. Although eccrine spiradenomas are usually benign, they can, on rare occasions, undergo malignant transformation. This case report describes one such occurrence of malignant transformation of a benign eccrine spiradenoma that unfortunately resulted in the patient's death from systemic metastases 7 months after diagnosis. [source] SQUAMOUS CELL PAPILLOMA OF THE ESOPHAGUS: CLINICOPATHOLOGICAL STUDY OF 24 CASESDIGESTIVE ENDOSCOPY, Issue 4 2004Junya Oguma Background:, Squamous cell papilloma of the esophagus is considered to be a rare condition; however, the number of cases with this condition reported in recent years has increased, perhaps due to advances in endoscopic diagnosis. Methods:, We reviewed the clinicopathological features of 26 lesions of squamous cell papilloma of the esophagus in 24 cases seen at our hospital from 1994 to 2003. There were nine men and 15 women, with a mean age of 60.5 years (range, 31,82 years). Six patients had a history of malignant disease in the past. With regard to the presence of other lesions in the esophagus, six patients had hiatal hernia and four had gastroesophageal re,ux disease. Results:, Two patients each had two lesions of squamous cell papilloma. There were seven lesions in which in,ammatory cell in,ltration was found on hisotological examination, of which four had underlying hiatal hernia; ,ve lesions were found to have mild dysplasia on histological examination of which three had gastroesophageal re,ux disease. The median duration of follow up of the cases was 8 months (range, 1,101 months). During the follow-up period, none of the lesions showed any dramatic change of appearance or malignant transformation. Conclusion:, In principle, while it may be suf,cient to keep patients with squamous cell papilloma of the esophagus under simple follow up, the patients must be investigated to rule out malignancy of other organs, and the small probability of malignant transformation of the tumor must always be borne in mind. [source] 5-Aminolaevulinic acid-induced photodynamic therapy and photodetection in Barrett's esophagusDISEASES OF THE ESOPHAGUS, Issue 3 2004P. E. Claydon SUMMARY., Barrett's esophagus is a precursor of adenocarcinoma of the esophagus. This cancer has the fastest growing incidence of any solid tumor in the Western world. Surveillance of Barrett's esophagus is routinely undertaken to detect early malignant transformation. However, ablative endoscopic treatments are available and these can obliterate the abnormal epithelium, allowing neosquamous regrowth. Photodynamic therapy using 5-aminolaevulinic acid (ALA) is such a technique. In this non-thermal method of ablation, ALA is metabolized to produce the photosensitizer protoprophyrin IX. This, together with light and oxygen, produces local tissue destruction. Fluorescence detection using ALA has also been used to identify areas of dysplasia and thus enhance positive biopsy yield. The use of ALA in photodynamic therapy and photodetection is reviewed. [source] Fas and Fas ligand expression on germinal center type-diffuse large B-cell lymphoma is associated with the clinical outcomeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2006Yasushi Kojima Abstract:, In recent years, diffuse large B-cell lymphoma (DLBCL) has been classified by DNA microarray analysis into the germinal center B-cell-like (GC) type, the activated B-cell-like (ABC) type and type 3. The latter two types can be collectively categorized as the non-GC (NGC) type. From the prognostic perspective, the GC type has a favorable clinical outcome when compared with the NGC type. The protein Fas induces apoptosis of lymphocytes by binding with the Fas ligand (FasL), and escape from such apoptosis is considered to lead to malignant transformation of the cells and unrestricted growth of lymphoma. We proposed a hypothesis that Fas/FasL expression could be possibly related with a better survival of GC type DLBCL and evaluated 69 DLBCL cases immunohistochemically with CD10, Bcl-6, MUM1, Fas and FasL. These lymphomas were classified as GC type (positive for CD10 or Bcl-6 and negative for MUM1) or NGC type. The GC type had a better overall survival rate than the NGC type (P = 0.0723). Among markers as given above, positive CD10 was the most significant prognostic factor for overall survival in total DLBCL (P < 0.05). In the GC type, Fas and FasL expressions were significantly associated with a favorable overall survival (Fas: P < 0.005; FasL: P < 0.05). Hence, Fas or FasL expression might contribute to a better prognosis of this type of DLBCL. [source] The molecular determinants of sunburn cell formationEXPERIMENTAL DERMATOLOGY, Issue 3 2001G. Murphy Abstract: Sunburn cell (SBC) formation in the epidermis is a characteristic consequence of ultraviolet radiation (UVR) exposure at doses around or above the minimum erythema dose. SBC have been identified morphologically and biologically as keratinocytes undergoing apoptosis. There is evidence that SBC formation is a protective mechanism to eliminate cells at risk of malignant transformation. The level of DNA photodamage is a major determinant of SBC induction by a process controlled by the tumor suppressor gene p53. However, extra-nuclear events also contribute to SBC formation, such as the activation of death receptors including CD95/Fas. UVR triggers death receptors either by direct activation of these surface molecules or by inducing the release of their ligands such as CD95 ligand or tumor necrosis factor. Oxidative stress also appears to be involved, probably via mitochondrial pathways, resulting in the release of cytochrome C. Pathways which modify SBC formation are now extensively studied given the importance of apoptosis in eliminating irreparably damaged cells. A greater understanding of the mechanisms that induce and prevent UVR-induced apoptosis will contribute to our understanding of mechanisms relevant in genomic integrity. [source] Cdt1 and geminin are down-regulated upon cell cycle exit and are over-expressed in cancer-derived cell linesFEBS JOURNAL, Issue 16 2004Georgia Xouri Licensing origins for replication upon completion of mitosis ensures genomic stability in cycling cells. Cdt1 was recently discovered as an essential licensing factor, which is inhibited by geminin. Over-expression of Cdt1 was shown to predispose cells for malignant transformation. We show here that Cdt1 is down-regulated at both the protein and RNA level when primary human fibroblasts exit the cell cycle into G0, and its expression is induced as cells re-enter the cell cycle, prior to S phase onset. Cdt1's inhibitor, geminin, is similarly down-regulated upon cell cycle exit at both the protein and RNA level, and geminin protein accumulates with a 3,6 h delay over Cdt1, following serum re-addition. Similarly, mouse NIH3T3 cells down-regulate Cdt1 and geminin mRNA and protein when serum starved. Our data suggest a transcriptional control over Cdt1 and geminin at the transition from quiescence to proliferation. In situ hybridization and immunohistochemistry localize Cdt1 as well as geminin to the proliferative compartment of the developing mouse gut epithelium. Cdt1 and geminin levels were compared in primary cells vs. cancer-derived human cell lines. We show that Cdt1 is consistently over-expressed in cancer cell lines at both the protein and RNA level, and that the Cdt1 protein accumulates to higher levels in individual cancer cells. Geminin is similarly over-expressed in the majority of cancer cell lines tested. The relative ratios of Cdt1 and geminin differ significantly amongst cell lines. Our data establish that Cdt1 and geminin are regulated at cell cycle exit, and suggest that the mechanisms controlling Cdt1 and geminin levels may be altered in cancer cells. [source] Down-regulation of the PI3-kinase/Akt pathway by ERK MAP kinase in growth factor signalingGENES TO CELLS, Issue 9 2008Hideko Hayashi The ERK MAP kinase and PI3-kinase/Akt pathways are major intracellular signaling modules, which are known to regulate diverse cellular processes including cell proliferation, survival and malignant transformation. However, it has not been fully understood how these two pathways interact with each other. Here, we demonstrate that inhibition of the ERK pathway by the MEK inhibitor U0126 or PD98059 significantly potentiates EGF- and FGF-induced Akt phosphorylation at both Thr308 and Ser473. We also show that hyperactivation of the ERK pathway greatly attenuates EGF- and FGF-induced Akt phosphorylation. Furthermore, the enhanced Akt phosphorylation induced by U0126 is inhibited by the PI3-kinase inhibitor LY294002, and is accompanied by the up-regulation of Ras activity. These results suggest that the ERK pathway inhibition enhances Akt phosphorylation through the Ras/PI3-kinase pathway. Thus, our results demonstrate that the ERK pathway negatively modulates the PI3-kinase/Akt pathway in response to growth factor stimulation. [source] Alteration of enhancer of polycomb 1 at 10p11.2 is one of the genetic events leading to development of adult T-cell leukemia/lymphomaGENES, CHROMOSOMES AND CANCER, Issue 9 2009Shingo Nakahata Adult T-cell leukemia/lymphoma (ATLL) is a malignant tumor caused by latent human T-lymphotropic virus 1 (HTLV-1) infection. We previously identified a common breakpoint cluster region at 10p11.2 in acute-type ATLL by spectral karyotyping. Single nucleotide polymorphism array comparative genomic hybridization analysis of the breakpoint region in three ATLL-related cell lines and four patient samples revealed that the chromosomal breakpoints are localized within the enhancer of polycomb 1 (EPC1) gene locus in an ATLL-derived cell line (SO4) and in one patient with acute-type ATLL. EPC1 is a human homologue of the E(Pc) enhancer of polycomb gene of Drosophila. Inappropriate expression of the polycomb group gene family has been linked to the loss of normal gene silencing pathways, which can contribute to the loss of cell identity and malignant transformation in many kinds of cancers. In the case of the SO4 cell line, which carried a der(10)t(2;10)(p23;p11.2) translocation, EPC1 was fused with the additional sex combs-like 2 (ASXL2) gene at 2p23.3 (EPC1/ASXL2). In the case with an acute-type ATLL, who carried a der(10)del(10)(p11.2)del(10)(q22q24) translocation, a putative truncated EPC1 gene (EPC1tr) was identified. Overexpression of EPC1/ASXL2 enhanced cell growth in T-leukemia cells, and a GAL4-EPC1/ASXL2 fusion protein showed high transcriptional activity. Although a GAL4-EPC1tr fusion protein did not activate transcription, overexpression of EPC1tr accelerated cell growth in leukemia cells, suggesting that the EPC1 structural abnormalities in the SO4 cell line and in the patient with acute-type ATLL may contribute to leukemogenesis. © 2009 Wiley-Liss, Inc. [source] Mechanisms of gene amplification and evidence of coamplification in drug-resistant human osteosarcoma cell linesGENES, CHROMOSOMES AND CANCER, Issue 4 2009Claudia M. Hattinger Gene amplification and copy number changes play a pivotal role in malignant transformation and progression of human tumor cells by mediating the activation of genes and oncogenes, which are involved in many different cellular processes including development of drug resistance. Since doxorubicin (DX) and methotrexate (MTX) are the two most important drugs for high-grade osteosarcoma (OS) treatment, the aim of this study was to identify genes gained or amplified in six DX- and eight MTX-resistant variants of the human OS cell lines U-2OS and Saos-2, and to get insights into the mechanisms underlying the amplification processes. Comparative genomic hybridization techniques identified amplification of MDR1 in all six DX-resistant and of DHFR in three MTX-resistant U-2OS variants. In addition, progressive gain of MLL was detected in the four U-2OS variants with higher resistance levels either to DX or MTX, whereas gain of MYC was found in all Saos-2 MTX-resistant variants and the U-2OS variant with the highest resistance level to DX. Fluorescent in situ hybridization revealed that MDR1 was amplified in U-2OS and Saos-2/DX-resistant variants manifested as homogeneously staining regions and double minutes, respectively. In U-2OS/MTX-resistant variants, DHFR was amplified in homogeneously staining regions, and was coamplified with MLL in relation to the increase of resistance to MTX. Gene amplification was associated with gene overexpression, whereas gene gain resulted in up-regulated gene expression. These results indicate that resistance to DX and MTX in human OS cell lines is a multigenic process involving gene copy number and expression changes. © 2008 Wiley-Liss, Inc. [source] Calcifying epithelial odontogenic (Pindborg) tumor with malignant transformation and metastatic spreadHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2001Michael J. Veness MB Abstract Background Pindborg tumors (calcifying epithelial odontogenic tumors) are uncommon neoplasms of odontogenic origin most often located in the posterior mandible. First described in detail in 1955 by Pindborg, these tumors are considered benign but can be locally aggressive in nature, with recurrence rates of 10% to 15% reported. The malignant form of this tumor is exceedingly rare. Methods We describe the case of a 64-year-old woman initially treated for a painful infected left mandibular third molar. The patient underwent extraction of the tooth and excision of an associated soft tissue component. Subsequent histologic review identified a Pindborg tumor of the left posterior mandible. Results After initial excision, this tumor recurred twice, with the recurrences exhibiting a progression to a malignant Pindborg tumor (odontogenic carcinoma) with vascular invasion and spread to a cervical lymph node. Further treatment involved radical surgery and adjuvant radiotherapy. At last review 12 months after treatment, the patient was disease free. Conclusions This article describes only the second case of odontogenic carcinoma. The transformation from benign to malignant histologic findings has not previously been documented in this tumor. The salient clinical features of this case are presented along with supportive pathologic and radiologic evidence. © 2001 John Wiley & Sons, Inc. Head Neck 23: 692,696, 2001. [source] Down-regulation of ATBF1 is a major inactivating mechanism in hepatocellular carcinomaHISTOPATHOLOGY, Issue 5 2008C J Kim Aims:, ,-Fetoprotein (AFP) is frequently detected in hepatocellular carcinomas (HCCs) and AT motif binding factor 1 (ATBF1) down-regulates AFP gene expression in hepatic cells. The ATBF1 gene also inhibits cell growth and differentiation, and altered gene expression is associated with malignant transformation. The aim was to investigate the potential role of the ATBF1 gene in HCCs. Methods and results:, Somatic mutations, allelic loss and hypermethylation of the ATBF1 gene were analysed in 76 sporadic HCCs. The level of ATBF-1 mRNA expression was analysed using quantitative real-time reverse transcriptase-polymerase chain reaction. Genetic studies of the ATBF1 gene revealed absence of somatic mutation in the hotspot region and 15 (25%) of 60 informative cases showed allelic loss at the ATBF1 locus. Hypermethylation in the intron 1 region of the ATBF1 gene was detected in only one case. Interestingly, ATBF1 mRNA expression in HCCs was significantly reduced in 55 (72.4%) samples compared with the corresponding surrounding liver tissues. Reduced expression was not statistically associated with clinicopathological parameters including stage, histological grade, infective virus type, and serum ,-fetoprotein level. Conclusions:, The ATBF1 gene may contribute to the development of HCCs via transcriptional down-regulation of mRNA expression, but not by genetic or epigenetic alterations. [source] Squamous cell carcinoma arising in mature cystic teratoma of the ovary: an immunohistochemical analysis of its tumorigenesisHISTOPATHOLOGY, Issue 1 2007A Iwasa Aims:, Squamous cell carcinoma (SCC) is the most common form of malignant transformation in mature cystic teratoma (MCT) of the ovary. Some investigators have suggested the possibility of origin from columnar epithelium. The aim of this study was to analyse such tumours immunohistochemically to elucidate their histogenesis. Methods and results:, The expression of cytokeratin (CK) 10 and CK18 was examined in 21 samples of SCC arising in MCT. The expression of CK10 and CK18 was also assessed in SCCs arising in different organs (skin, vulva, lung and uterine cervix) for the purpose of comparison. SCC in MCT expressed CK10 in 7/21 cases [33.3%, 95% confidence interval (CI) 0.12,0.53] and CK18 in 14/21 cases (66.7%, 95% CI 0.46,0.87). SCC in MCT expressed CK10 less frequently, but CK18 more frequently, as is the case in SCCs of the uterine cervix (CK10, 20%; CK18, 70%) and the lung (CK10, 5%; CK18, 90%), both of which are derived from columnar epithelium by squamous metaplasia. Conclusions:, SCC in MCT may be derived from metaplastic squamous epithelium. [source] The increased expression of Y box-binding protein 1 in melanoma stimulates proliferation and tumor invasion, antagonizes apoptosis and enhances chemoresistanceINTERNATIONAL JOURNAL OF CANCER, Issue 10 2007Birgit Schittek Abstract In previous studies we identified the transcription/translation factor Y-box-binding protein (YB-1) as a gene that is upregulated in primary melanoma and melanoma metastases when compared to benign melanocytic nevi. To analyze whether YB-1 expression correlates with melanoma progression in vitro and in vivo, we performed expression analysis on melanoma cell lines representing different stages of melanoma progression and on tissues of melanocytic nevi, primary melanoma and melanoma metastases. Our data indicate that compared to benign melanocytes YB-1 expression is increased in melanoma cells in vitro and in vivo and that YB-1 is translocated into the nucleus in invasive and metastatic melanoma cells. To reveal the functional role of YB-1 in melanoma progression we achieved a stable downregulation of YB-1 using shRNA in metastatic melanoma cells. Interestingly, YB-1 downregulation resulted in a pronounced reduced rate of proliferation and an increased rate of apoptotic cell death. In addition, migration and invasion of melanoma cells in monolayer and in a three-dimensional skin reconstruct in vitro was significantly reduced. These effects were accompanied by downregulation of genes involved in proliferation, survival and migration/invasion of melanoma cells such as MMP-2, bcl-2, Cyclin D1, p53 and p16INK4A. Furthermore, melanoma cells with a reduced YB-1 expression showed a decreased resistance to the chemotherapeutic agents cisplatin and etoposide. These data suggest that YB-1 is involved in malignant transformation of melanocytes and contributes to the stimulation of proliferation, tumor invasion, survival and chemoresistance. Thus, YB-1 may be a promising molecular target in melanoma therapy. © 2007 Wiley-Liss, Inc. [source] Alterations in tropomyosin isoform expression in human transitional cell carcinoma of the urinary bladderINTERNATIONAL JOURNAL OF CANCER, Issue 3 2004Geraldine Pawlak Abstract Previous studies of transformed rodent fibroblasts have suggested that specific isoforms of the actin-binding protein tropomyosin (TM) could function as suppressors of transformation, but an analysis of TM expression in patient tumor tissue is limited. The purpose of our study was to characterize expression of the different TM isoforms in human transitional cell carcinoma of the urinary bladder by immunohistochemistry and Western blot analysis. We found that TM1 and TM2 protein levels were markedly reduced and showed >60% reduction in 61% and 55% of tumor samples, respectively. TM5, which was expressed at very low levels in normal bladder mucosa, exhibited aberrant expression in 91% of tumor specimens. The Western blot findings were confirmed by immunohistochemical analysis in a number of tumors. We then investigated the mechanism underlying TM expression deregulation, in the T24 human bladder cancer cell line. We showed that levels of TM1, TM2 and TM3 are reduced in T24 cells, but significantly upregulated by inhibition of the mitogen-activated protein kinase-signaling pathway. In addition, inhibition of this pathway was accompanied by restoration of stress fibers. Overall, changes in TM expression levels seem to be an early event during bladder carcinogenesis. We conclude that alterations in TM isoform expression may provide further insight into malignant transformation in transitional cell carcinomas of the bladder and may be a useful target for early detection strategies. © 2004 Wiley-Liss, Inc. [source] Cyclin E expression in papillary thyroid carcinoma: Relation to stagingINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Jan Brzezi Abstract Cyclin E plays a pivotal role in the regulation of G1-S transition and relates to malignant transformation of the cells. However, the clinical significance of cyclin E expression in patients with papillary thyroid carcinoma (PTC) remains unknown. We examined by immunohistochemistry the expression of cyclin E in 41 resected PTCs in pathologic stages from pT1a to pT4 and analyzed its relation to clinicohistopathologic factors. The positive staining was divided into 3 grades: no expression if less than 10%, expression if 11,50% and overexpression if more than 50% of the nuclei of tumor cells were stained positively. Cylin E expressions were observed in 75.6% of analyzed PTCs but only 60% of papillary microcarcinomas (PMCs) were immunopositive for cyclin E expression. However, cyclin E staining was observed in 90.4% of PTCs in a group with TNM higher than pT1a. The staining index was significantly different between the PMCs and the rest of the cancers investigated (14.91% ± 14.4% vs. 34.03% ± 23.44%, respectively; p < 0.005) and we observed positive relation between the staining index and factor T of staging of PTCs. All the lymph node metastases coexisted with cyclin E expression and most, but not all, of them coexisted with cyclin E overexpression. These findings indicate that cyclin E may play a key role for the oncogenesis and biologic behavior of PTC. If our results are confirmed in a larger study, a high level of cyclin E expression may become a new prognostic marker for PTCs. © 2003 Wiley-Liss, Inc. [source] The effect of desalivation on the malignant transformation of the tongue epithelium and associated stromal myofibroblasts in a rat 4-nitroquinoline 1-oxide-induced carcinogenesis modelINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2010Marilena Vered Summary The aim of our study was to analyse desalivated rat tongue epithelium for histopathological changes, proliferating cell nuclear antigen (PCNA), and epithelium-associated stromal myofibroblasts [SMF; ,-smooth muscle actin (,SMA)] following 0.001% 4-nitroquinoline 1-oxide (4NQO) administration in drinking water. Results were compared with those of identically treated but salivated specimens. 4NQO was administered for 7, 14, 22 and 28 weeks. Tongue length was divided into anterior, middle and posterior ,thirds'. The histopathological changes per ,third' were scored as normal epithelium, hyperplasia, dysplasia, carcinoma- in-situ, and superficial and invasive carcinoma. The PCNA and ,SMA stains were assessed by a point-counting method. At all time points, the histopathological changes in the anterior and middle thirds were higher in the desalivated than in the salivated group (P < 0.05) but almost identical in the posterior third (P > 0.05). PCNA scores were significantly lower in the desalivated vs. the salivated group at almost all time points and tongue thirds (P < 0.05). SMF were usually scarce in both groups, but there was a significant surge in the posterior third at 28 weeks: the score in the desalivated group was only about one-half that of the salivated group (P < 0.05). The absence of saliva seems to promote malignant transformation of the tongue epithelium in the early stages. PCNA cannot be regarded as a marker of proliferation and probably contributes to this process by other mechanisms. Emergence of SMF seems to be highly dependent on growth factors from saliva in addition to factors from cancerous cells. [source] Overexpression of Fos-related antigen-1 in head and neck squamous cell carcinomaINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2005Flavia R. R. Mangone Summary The activating protein-1 (AP-1) family of transcription factors has been implicated in the control of proliferation and differentiation of keratinocytes, but its role in malignant transformation is not clear. The aim of this study is to assess the pattern of mRNA expression of jun-fos AP-1 family members in 45 samples of head and neck squamous cell carcinomas (HNSCC) and matched adjacent mucosa by means of Northern blot analysis. Transcripts of all family members were identified, except for JunB that was detected only by means of reverse transcription polymerase chain reaction. Neither c-Fos nor JunD or FosB mRNA differed between tumours and normal tissues. We observed a strong Fos-related antigen-1 (Fra-1) and Fra-2 expression, but only Fra-1 mRNA densitometric values were higher in tumour, compared to normal adjacent mucosa (t -test, P = 0.006). A direct relationship between the positive expression of Fra-1 mRNA, above tumour median, was associated with the presence of compromised lymph nodes (Fischer exact test, P = 0.006). In addition, Fra-1 protein staining was assessed in a collection of 180 tumours and 29 histologically normal samples adjacent to tumours in a tissue array. Weak reactivity, restricted to the basal cell layer, was detected in 79% of tumour adjacent normal tissues, opposed to the intense reactivity of cancer tissues. In the subgroup of oral cancers, we have observed a shift in Fra-1 immunoreactivity, as long as the number of patients in each category, cytoplasmic or nuclear/cytoplasmic staining, was analysed (Fischer exact test, P = 0.0005). Thus, Fra-1 gene induction and accumulation of Fra-1 protein may contribute to the neoplastic phenotype in HNSCC. [source] Osteopontin: a key cytokine in cell-mediated and granulomatous inflammationINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 6 2000Anthony O'Regan Osteopontin (Opn) is a secreted adhesive, glycosylated phosphoprotein that contains the arginine-glycine-aspartic acid (RGD) cell-binding sequence that is found in many extracellular matrix (ECM) proteins (for a review of Opn see References Denhardt & Guo 1993; Patarca et al. 1993; Rittling & Denhardt 1999). Since its initial description in 1979 as a secreted protein associated with malignant transformation, Opn has been independently discovered by investigators from diverse scientific disciplines, and has been associated with a remarkable range of pathologic responses. Opn is an important bone matrix protein, where it is thought to mediate adhesion of osteoclasts to resorbing bone. However, studies from the past decade have identified an alternative role for Opn as a key cytokine regulating tissue repair and inflammation. Recent work by our laboratory and that of others has underlined the importance of Opn as a pivotal cytokine in the cellular immune response. Despite this Opn is not well known to the immunologist. In this review we will focus on studies that pertain to the role of Opn in cell-mediated and granulomatous inflammation. [source] | ||||||||||||||||||||||||||||||||||||||||