1/34. Characterization of human MMTV-like (HML) elements similar to a sequence that was highly expressed in a human breast cancer: further definition of the HML-6 group.Previously, we found a retroviral sequence, HML-6.2BC1, to be expressed at high levels in a multifocal ductal breast cancer from a 41-year-old woman who also developed ovarian carcinoma. The sequence of a human genomic clone (HML-6.28) selected by high-stringency hybridization with HML-6.2BC1 is reported here. It was 99% identical to HML-6.2BC1 and gave the same restriction fragments as total dna. HML-6.28 is a 4.7-kb provirus with a 5'LTR, truncated in RT. Data from two similar genomic clones and sequences found in GenBank are also reported. Overlaps between them gave a rather complete picture of the HML-6.2BC1-like human endogenous retroviral elements. work with somatic cell hybrids and FISH localized HML-6.28 to chromosome 6, band p21, close to the MHC region. The causal role of HML-6.28 in breast cancer remains unclear. Nevertheless, the ca. 20 Myr old HML-6 sequences enabled the definition of common and unique features of type A, B, and D (ABD) retroviruses. In Gag, HML-6 has no intervening sequences between matrix and capsid proteins, unlike extant exogenous ABD viruses, possibly an ancestral feature. Alignment of the dUTPase showed it to be present in all ABD viruses, but gave a phylogenetic tree different from trees made from other ABD genes, indicating a distinct phylogeny of dUTPase. A conserved 24-mer sequence in the amino terminus of some ABD envelope genes suggested a conserved function.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/34. Well-differentiated mucinous carcinoma of the ovary and a coexisting brenner tumor both exhibit amplification of 12q14-21 by comparative genomic hybridization.Although the coexistence of mucinous ovarian neoplasms and Brenner tumors is well established, the histogenesis and developmental relationship between the two remain unknown. We used comparative genomic hybridization to analyze two such tumors occurring simultaneously, one in each ovary, in a patient. Amplification of 12q14-21 sequences was found in both tumors; in addition, both tumors also had other, different changes, four identified in the brenner tumor and six in the mucinous carcinoma. The occurrence of the same genetic alteration in both tumors in this woman suggests that the mucinous carcinoma and brenner tumor may be clonally related, i.e., one arose from the other by means of metastatic spreading of transformed cells from one ovary to the other. An alternative explanation is that some unknown, putative tumorigenic agent induced similar and synchronous pathogenetic changes in the epithelium of both ovaries. The phenotypic differences between the tumors are presumably attributable to the other unique genetic abnormalities identified in both tumor types.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
3/34. trisomy 8 as sole karyotypic aberration in an ovarian metastasizing sertoli-leydig cell tumor.Sertoli-Leydig cell tumors (SLCTs) represent a rare group of sex-cord stromal tumors of the ovary of unknown pathogenesis. We report a SLCT of intermediate differentiation with peritoneal recurrence and lymph node metastasis 12 months after removal, including cytogenetic analysis by comparative genomic hybridization and fluorescence in situ hybridization, which showed trisomy 8 as sole unbalanced karyotypic aberration. Our results provide evidence that a simple numeric chromosomal abnormality in SLCT may be associated with a malignant phenotype and suggest that the molecular pathogenesis of SLCT may be different from ovarian granulosa-stromal cell tumors.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
4/34. collagen type xviii/endostatin is differentially expressed in primary and metastatic colorectal cancers and ovarian carcinomas.collagen type xviii (C18) is a nonfibrillar collagen of basement membranes. Its C-terminal fragment, endostatin, has been identified as an inhibitor of angiogenesis. C18 is predominantly expressed by hepatocytes of normal, cirrhotic and neoplastic liver. We compared the patterns of C18 rna-expression in colonic adenocarcinoma metastases, which represent the most frequently occurring liver tumours, to normal colon mucosa, to primary colon cancers and to ovarian cancers which are often morphologically similar to colonic cancer or metastasis. Two C18-specific rna-probes were generated to perform in situ hybridization combined with immunohistochemistry for cytokeratin, vimentin and the endothelial marker CD31, in order to characterize the C18-expressing cells. C18/endostatin protein was localized by immunohistology. In colorectal carcinomas and their liver metastases high levels of C18 transcripts were observed in endothelial cells and fibroblasts/myofibroblasts, whereas C18 rna was virtually absent from carcinoma cells. Ovarian carcinomas displayed high C18 rna expression both in carcinoma and stromal cells, indicating that induction of C18 transcription in tumour stromal cells is independent of the ability of carcinoma cells to express C18. While the role of tumour cell derived C18 in cancer growth regulation remains unknown, stimulation of proteolysis of the locally strongly expressed C18 to endostatin could offer an attractive approach for a targeted antineoplastic therapy.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/34. fibrosarcoma associated with a benign cystic teratoma of the ovary.OBJECTIVE: A case of ovarian fibrosarcoma associated with a benign cystic teratoma is described. methods: A 32-year-old patient with an ovarian tumor detected by routine gynecological examination was referred to our hospital. In addition to histopathological examination of the resected tumor, immunohistochemical studies as well as a cytogenetic analysis by comparative genomic hybridization were carried out. RESULTS: The 7-cm-sized tumor consisted of two different components: a fibrosarcoma and a benign cystic teratoma. The teratoma contained elements of all three germ layers and lacked any focus of immature teratoma. A fibrosarcoma was immediately connected to the teratoma. The sarcoma cells showed eight mitoses per 10 high-power fields on average and exhibited immunohistochemical reactivity for vimentin only. cytogenetic analysis of the fibrosarcoma using comparative genomic hybridization revealed imbalances of chromosomes 9, 12, and 16. After a 1-year follow-up, there were no signs of tumor recurrence or systemic disease. CONCLUSION: To the authors' knowledge, this is the second report of an association of ovarian fibrosarcoma and benign cystic teratoma, and the first including a cytogenetic analysis.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
6/34. Hypercalcemic-type of small cell carcinoma of the ovary: characterization of a new tumor line.BACKGROUND: The aim of this study was to develop and characterize a mouse xenograft model for the hypercalcemic-type of small cell carcinoma of the ovary (HTSCCO). patients AND methods: Tumor fragments were removed from a patient and cultured in six subsequent generations of nude mice. Histology, comparative genomic hybridization (CGH), electron microscopy and serum calcium levels were investigated. RESULTS: Morphology remained the same from the primary tumor of the patient through the 6th passage in the mouse. serum calcium levels were significantly higher in the tumor-bearing mice compared to controls. CGH of the HTSCCO did not show evidence of a close relationship to either a germ cell tumor or an epithelial ovarian cancer. CONCLUSION: Some evidence was provided that the HTSCCO is an inhomogeneous tumor that is neither related to a germ cell tumor nor to an epithelial ovarian cancer, but is a distinct tumor entity.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/34. Comprehensive cytogenetic evaluation of a mature ovarian teratoma case.Mature ovarian teratomas are benign ovarian germ cell tumors that usually present with a normal karyotype. There are very few reports describing chromosomal abnormalities in these tumors, none of which are recurrent. In this study we report on a mature teratoma case with clonal chromosomal alterations which include monosomies of chromosomes 6, 14, 16, and 21; trisomies of chromosomes 14 and 21; and deletions of Xq, 5p, 16p, and 17p. comparative genomic hybridization evaluation of the sample revealed a normal profile. These findings are discussed together with the cytogenetic reports on other cases of ovarian teratomas described in the literature.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/34. Familial ovarian dysgerminomas (Swyer syndrome) in females associated with 46 XY-karyotype.An asymptomatic woman (age 38 years) with a family history of ovarian malignancies was referred for presymptomatic genetic testing of mutations in the BRCA genes. A familial Swyer syndrome with the occurrence of dysgerminomas is the most likely diagnosis. However, in our case, all known causes of this heterogeneous disorder have been excluded pointing to the existence of another yet unknown genetic locus. The family history revealed three affected paternal aunts. Two of them developed ovarian malignancies at 13 and 15 years of age, and died at ages 19 and 20. The third aunt, 82 years old, was affected by this disease at the age of 35. She underwent hormonal treatment for 3 years starting at the age of 15 because of primary amenorrhea. Under this treatment she developed nearly complete secondary sexual characteristics. karyotype analysis revealed a normal male karyotype (46 XY, QFQ). Pelvic ultrasound showed an uterus of normal size, incompatible with an androgen resistance syndrome or a defect in testosterone biosynthesis. We excluded a mutation in the sex-determining region on chromosome Y (SRY) by direct sequencing of the SRY gene. An involvement of the subtelomeric region of chromosome 9p (9p 24.3) recently reported to be involved in XY-sex reversal phenotypes was excluded by molecular testing for loss of heterozygosity as well as fluorescence in situ hybridization studies. Analyses of the DAX1 gene in the dosage sensitive sex reversal locus on chromosome Xp21 by Southern blot analysis showed no duplications.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
9/34. Ovarian carcinomas in endometriosis: an immunohistochemical and comparative genomic hybridization study.Malignant transformation of endometriosis, an uncommon phenomenon, can occur in gonadal and extragonadal sites and results in a wide histological range of tumors. Published series reporting malignant transformation of endometriosis have largely been confined to clinical and histopathological discussions with no studies reporting oncoprotein expression and genetic alterations. We report three cases of carcinomas arising in ovarian endometriosis: a serous cystadenocarcinoma, an endometrioid carcinoma with squamous differentiation, and a pure squamous cell carcinoma. Each tumor was analyzed immunohistochemically to compare oncoprotein expression (p53, bcl2, cyclin d1, and c-erb B2) between the tumors and the endometriotic tissue as well as with comparative genomic hybridization (CGH) to compare genetic alterations. All three tumors expressed nuclear p53, in contrast to the endometriotic tissue in which no p53 expression was found. Both endometrial and tumor tissue expressed bcl-2. No expression of cyclin d1 or c-erb B2 was detected in endometriotic or tumoral tissues. The CGH analysis revealed one or two chromosomal aberrations in each of the three tumors with gains on chromosomes 1q, 8q, and 13q, and losses on chromosome 10p. The endometriotic tissue, as expected, showed a normal genetic profile. These results suggest that p53 protein abnormalities and chromosomal aberrations may be involved in malignant transformation of endometriosis in the ovary. However, our results are limited by the number of cases examined and a definite conclusion on the pathogenesis of this process should be followed by future studies with a larger number of cases.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
10/34. Metastatic endocervical adenocarcinoma presenting as a virilizing ovarian mass during pregnancy.BACKGROUND: We report a case of metastatic endocervical adenocarcinoma that presented as a virilizing ovarian mass in a young pregnant woman and simulated a primary ovarian endometrioid tumor. CASE: A 34-year-old woman underwent cesarean delivery and right salpingo-oophorectomy at 34 weeks' gestation for a 32-cm androgen-producing ovarian mass. The ovarian tumor, initially interpreted as a primary ovarian endometrioid carcinoma, was demonstrated to represent metastatic endocervical endometrioid adenocarcinoma based on detection of human papillomavirus 16 (HPV-16) deoxyribonucleic acid in the tumor by in situ hybridization. The hysterectomy specimen demonstrated an endocervical adenocarcinoma associated with adenocarcinoma in situ that also contained HPV-16. CONCLUSION: Human papillomavirus is considered an etiological agent in the development of endocervical adenocarcinomas, having been demonstrated in greater than 90% of tumors. In contrast, recent studies have concluded that HPV is unlikely to play an etiological role in ovarian neoplasia. The demonstration of HPV-16 in both the endocervical and ovarian carcinomas in this patient supports the interpretation that the ovarian tumor is a metastasis.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
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