Common Epithelial Tumors Of Ovary Research Articles

Immunohistochemical Characterization of Normal Ovary and Common Epithelial Ovarian Neoplasm with a Monoclonal Antibody to Cytokeratin and Vimentin

The common epithelial ovarian tumors are classified into serous, mucinous, clear cell, endometrioid, the Brenner, mixed, and undifferentiated types. Cytoskeleton intermediate filament composition of ovarian tissues indicates that the cytokeratin and vimentin are observed in ovarian surface epithelium along with the common ovarian epithelial tumors. The current study aimed at investigating the cytokeratin and vimentin expression in epithelial ovarian tumors to establish a diagnostic relevance. Sixty-six common epithelial ovarian tumors were studied using anti-cytokeratins (Monoclonal Mouse Anti-Human Cytokeratin Clones AE1/AE3; DAKO, Denmark,) and anti-vimentin (Monoclonal Mouse Anti-Vimentin, Clone V9; DAKO, Denmark,) to ascertain the intermediate filament profiles in formalin-fixed and paraffin-embedded surgical pathology materials. All ovarian epithelial tumors expressed cytokeratin in a uniform fashion. Vimentin was coexpressed with high intensity in 62.5% of serous carcinomas, mild intensity in 25% of mucinous adenocarcinoma, and moderate intensity in single case of endometrioid adenocarcinoma. Vimentin decoration in mucinous carcinoma had a focal involvement, whereas malignant endometrioid and serous decoration tended to involve larger areas. There was a significantly increased expression of vimentin in serous cystadenoma and serous carcinoma, compared with their mucinous counterparts. Also, vimentin expression and histologic grade of serous tumors showed a positive correlation. No association was found between vimentin expression and degree of differentiation in mucinous, endometrioid, and Brenner tumors. The current investigation emphasized the efficiency of immunohistochemistry (IHC) typing as a tool for a more precise characterization of the origin and differentiation of human neoplasms.

AN UNUSUAL CYTOLOGICAL EXPERIENCE OF VIRILISING OVARIAN SERTOU-LEYDIG CELL TUMOR - A RARE CASE REPORT

AbstractSertoli-Leydig cell tumor of ovary is a gonadal tumour of the sex cord-stromal type. It is a rare tumor comprising 0.1 to 0.5% of all ovarian tumours. Peritoneal cytology has been well established as a diagnostic and staging tool in the management of the common epithelial tumours of ovary. Germ cell, mesenchymal, and sex-cord stromal tumours are much less frequently encountered in peritoneal specimens, often with cytologic features that may pose diagnostic difficulty and dilemma. We report a case of peritoneal fluid cytology of sertoli leydig cell tumor of ovary in a 20 year old female who presented with virilising symptoms. On removal of ovarian tumor, her virilising symptoms regressed, with regaining of menstruation.

Immunolocalization of Nuclear Transcription Factors, DAX-1 and Ad4BP/SF-1, in Human Common Epithelial Ovarian Tumors: Correlations With StAR and Steroidogenic Enzymes in Epithelial Ovarian Carcinoma

Intratumoral steroidogenesis is considered to play important roles in the biologic behavior of common epithelial ovarian carcinoma. Recent studies have demonstrated the important roles of Ad4BP/SF-1 and DAX-1 in regulation of steroidogenesis. In this study, we evaluated DAX-1, Ad4BP/SF-1, StAR, and steroidogenic enzyme expressions and their correlations in epithelial ovarian carcinomas to evaluate the possible roles of these factors in regulation of intratumoral steroid metabolism and/or production. Immunolocalization of DAX-1, Ad4BP/SF-1, StAR, and steroidogenic enzymes were examined in 90 epithelial ovarian carcinomas. mRNA expression of these proteins was evaluated using real-time polymerase chain reaction (PCR) in 23 cases for further characterization. DAX-1 and Ad4BP/SF-1 immunoreactivity was detected predominately in the nuclei of tumor cells, whereas that of StAR and steroidogenic enzymes was present in the cytoplasm. We detected a significant positive correlation between StAR and steroidogenic enzymes immunoreactivity and Ad4BP/SF-1 and statistically inversed correlation with DAX-1. A positive statistical correlation was detected between intratumoral stromal Ad4BP/SF-1 immunoreactivity and clinicopathologic parameters of carcinoma patients. Results of real-time PCR analysis were correlated with those of immunohistochemical studies. The status of intratumoral DAX-1, Ad4BP/SF-1, and StAR and steroidogenic enzymes in epithelial cells and intratumoral stromal cells of epithelial ovarian carcinoma may contribute in the progression and/or aggressiveness of these tumors.

Immunohistochemical study of fatty acid synthase in ovarian neoplasms.

In order to evaluate the prognostic significance of fatty acid synthase (FAS), the key enzyme in fatty acid biosynthesis, in ovarian benign and malignant tumors 98 patients with ovarian masses were immunohistochemically evaluated. Histologic features of the lesions and expression for FAS were statistically associated with clinical data and disease-free survival over a 5-year follow-up period. The mean age of patients was 65 years. TNM surgical stages were I in 31.8%, II in 28.2% and III in 40% of cases. The 5-year disease-free survival of the 85 malignant common epithelial ovarian tumors was 47.1% while 35.3 of patients died with active disease. Seventy-eight (79.6%) out of 98 cases expressed FAS in the neoplastic epithelial cells and 42 (42.9%) in the non-neoplastic stromal cells. Statistical analysis revealed FAS expression and stage of the disease to be significantly correlated to recurrence and survival rates only in the malignant common epithelial tumors. Moreover, multivariate analysis showed FAS expression (p=0.05) and tumor stage (p=0.03) to be independent prognostic predictors. FAS is a reliable predictor of recurrence and disease-free survival in common epithelial ovarian tumors along with neoplastic stage. Clinical data, other histologic subtypes and grading were not statistically significant.

Expression of E-cadherin and N-cadherin in surface epithelial-stromal tumors of the ovary distinguishes mucinous from serous and endometrioid tumors

This study examines the expression of E-cadherin and N-cadherin in the most common epithelial tumors of the ovary. The homotypic interactions of distinctive members of the cadherin family of cell-cell adhesion molecules segregate cells into tissues during embryonic development, and their expression in tumors can be used to trace the histogenesis of tumor cells. Because the surface epithelium of the ovary is a modified mesothelium, we speculated that the expression of E (epithelial)-cadherin and N (neural, mesodermal) -cadherin may provide clues about the controversial origin of common epithelial ovarian tumors. Immunohistochemistry was performed in paraffin sections using well-characterized monoclonal antibodies to E- and N-cadherin and heat-induced antigen-retrieval methods. We found that serous and endometrioid tumors express both E- and N-cadherin. In contrast, mucinous tumors strongly express E-cadherin, but no N-cadherin. The presence of N-cadherin in serous and endometrioid tumors traces their origin to the mesoderm-derived ovarian surface epithelium. The absence of N-cadherin in mucinous tumors clearly distinguishes them from the former, suggesting histogenesis from a cell lineage other than the ovarian surface epithelium or aberrant differentiation mechanisms associated with neoplastic transformation.

Alteration of p16 and p15 genes in common epithelial ovarian tumors

We have examined the roles of 2 putative tumor-suppressor genes, the p16 and p15 inhibitor-of-cyclin-dependent-kinase genes, in the most commonly occurring epithelial tumors of the human ovary. Expression of p16 mRNA, examined by RT-PCR, was significantly reduced in 15 of the 48 tumors. Aberrant expression of p16 protein, detected by immunohistochemistry, occurred in 22 of 60 tumors, more frequently in low-grade tumors, and had significant correlation with low p16 mRNA expression. Hypermethylation of a site within the 5′-CpG island of the p16 gene was significantly associated with loss of p16 mRNA and protein expression. Homozygous gene deletion, evaluated by differential PCR analysis, was found in 2 tumors for the p16 gene and in 1 tumor for the p15 gene among 70 ovarian tumors examined. PCR-SSCP analysis detected point mutations in p16 in 4 tumors and in p15 in 1 tumor. One was a 38-bp deletion, from codons 48 to 60, in a mucinous tumor of low malignant potential; another was a non-sense mutation in codon 60 in a mucinous adenocarcinoma. The remaining 2 mutations were mis-sense mutations, one in codon 58 and the other in codon 60, in 2 endometrioid adenocarcinomas. We conclude that inactivation of p16, by loss of p16 mRNA and protein expression as a consequence of hypermethylation of the 5′-CpG island, rather than by gene deletion or point mutation, may play an important role in the genesis of human ovarian epithelial tumors. Int. J. Cancer 74:148-155, 1997. © 1997 Wiley-Liss, Inc.

Alteration of p16 and p15 genes in common epithelial ovarian tumors.

We have examined the roles of 2 putative tumor-suppressor genes, the p16 and p15 inhibitor-of-cyclin-dependent-kinase genes, in the most commonly occurring epithelial tumors of the human ovary. Expression of p16 mRNA, examined by RT-PCR, was significantly reduced in 15 of the 48 tumors. Aberrant expression of p16 protein, detected by immunohistochemistry, occurred in 22 of 60 tumors, more frequently in low-grade tumors, and had significant correlation with low p16 mRNA expression. Hypermethylation of a site within the 5'-CpG island of the p16 gene was significantly associated with loss of p16 mRNA and protein expression. Homozygous gene deletion, evaluated by differential PCR analysis, was found in 2 tumors for the p16 gene and in 1 tumor for the p15 gene among 70 ovarian tumors examined. PCR-SSCP analysis detected point mutations in p16 in 4 tumors and in p15 in 1 tumor. One was a 38-bp deletion, from codons 48 to 60, in a mucinous tumor of low malignant potential; another was a non-sense mutation in codon 60 in a mucinous adenocarcinoma. The remaining 2 mutations were mis-sense mutations, one in codon 58 and the other in codon 60, in 2 endometrioid adenocarcinomas. We conclude that inactivation of p16, by loss of p16 mRNA and protein expression as a consequence of hypermethylation of the 5'-CpG island, rather than by gene deletion or point mutation, may play an important role in the genesis of human ovarian epithelial tumors.

Expression of epidermal growth factor-related proteins and epidermal growth factor receptor in common epithelial ovarian tumors.

The biologic significance of epidermal growth factor (EGF)-related proteins and EGF receptor (EGFR) in the development and progression of human ovarian carcinoma was studied in 7 ovarian cystadenomas, 6 mucinous tumors of low malignant potential (LMP), and 25 invasive adenocarcinomas by immunohistochemistry. Results were correlated with clinicopathologic features. We also examined immunoreactivity in five serous adenocarcinomas both before and after cisplatin chemotherapy. Amphiregulin (AR) expression was observed only in mucinous tumors (4 of 8 cystadenomas, 2 of 6 tumors of LMP, and 6 of 10 cystadenocarcinomas), but was not detected in the serous tumors or clear cell adenocarcinomas. EGF, cripto, and EGFR expression was significantly higher in mucinous cystadenocarcinomas than in mucinous cystadenomas or mucinous tumors of LMP. Three of five specimens obtained at a second operation after chemotherapy had more intense or diffuse immunostaining for transforming growth factor alpha (TGF-alpha) than the initial specimens did. Coexpression of more than two of the EGF-related proteins or EGFR significantly correlated with increased surgical stage in serous and clear cell carcinoma. AR expression seems to correlate with mucinous differentiation rather than with advanced stages of ovarian tumors. Our results indicate that expression of some EGF-related proteins is greater in certain subtypes of ovarian carcinomas than in their benign counterparts and that coexpression of these proteins is associated with advanced stage in serous and clear cell carcinoma. Increased TGF-alpha expression may also be related to ovarian tumor resistance to cisplatin chemotherapy.

Alteration of the p53 tumor suppressor gene occurs independently of K-ras activation and more frequently in serous adenocarcinomas than in other common epithelial tumors of the human ovary.

To clarify the role of the p53 tumor suppressor gene in the development of human ovarian epithelial tumors and to study the association of p53 alterations with K‐ras activation, a series of 70 common epithelial ovarian tumors from Japanese patients was studied. These included 31 serous adenocarcinomas, 12 mucinous adenocarcinomas, 5 mutinous tumors of borderline malignancy, 13 endometrioid adenocarcinomas, and 9 clear cell carcinomas. Allelic loss, recognized at the polymorphic site in codon 72 of the p53 gene, was detected in 14 of 36 (39%) informative cases by restriction fragment length polymorphism analysis and by single‐strand conformation polymorphism (SSCP) analysis of polymerase chain reaction(PCR)‐amplified DNA fragments. Mutations in the highly conserved regions of the p53 gene were detected by SSCP analysis of PCR‐amplifled fragments. Mutations were found in 22 of 70 (31%) ovarian tumors, including 1 of 5 mucinous tumors of borderline malignancy. Mutations were subsequently characterized by direct sequencing. Single missense base substitutions were detected in 13 ovarian carcinomas and in one case of mucinous tumor of borderline malignancy. Short (1‐8 bp) deletions and insertions were found in 8 cases. Mutations in the p53 gene occurred more frequently in serous adenocarcinomas (14/31, 45%) than in all nonserous types of malignant epithelial tumors combined (7/34, 21%;P=0.032). Point mutations in K‐ras were identified by dot blot hybridization analysis of PCR‐amplified fragments with mutation‐specific oligonucleotides and by direct sequencing. The overall frequency of K‐ras mutations was 19/70 (27%).K‐ras mutations were found in 12 of 17 (71%) mucinous tumors (8/12 mucinous carcinomas [67%] and 4/5 mucinous tumors of borderline malignancy [80%]), and occurred more frequently than in serous carcinomas (4/31, 13%;P=0.00009) or in all nonmucinous types of ovarian epithelial tumors combined (7/53, 13%; p=0.00002). These data suggest that different combinations of oncogenes and/or tumor suppressor genes may be involved in the genesis and development of histologically distinct categories of common epithelial tumors of the human ovary.

Peritoneal cytology of uncommon ovarian tumors

Peritoneal cytology has been well established as a diagnostic and staging tool in the management of the common epithelial tumors of ovary. Germ cell, mesenchymal, and sex-cord stromal tumors are much less frequently encountered in peritoneal specimens, often with cytologic features that may pose problems in differential diagnosis. This report presents the cytomorphology of the ascitic fluid in cases of endodermal sinus tumor, dysgerminoma, and Sertoli-Leydig-cell tumor, and peritoneal washings in a case of ovarian malignant mixed mullerian tumor. The cytologic features of Sertoli-Leydig-cell tumors have not been well described. Careful correlation of peritoneal cytologic findings, cell-block preparations, and immunocytochemistry with the cytohistologic features of these tumors is crucial for correct tumor classification.

Lectin Binding to Common Epithelial Tumors of the Ovaries

Binding sites of peanut agglutinin (PNA), Ulex europaeus (UEA-1), wheat germ agglutinin, concanavalin A, and Ricinus communis were localized in 46 common epithelial ovarian tumors. Binding pattern of serous cystadenomas showed significant similarity with the pattern seen in the epithelium of fallopian tubes. Lectin affinity of endometriosis and endometrioid tumors was similar to normal endometrium in secretory phase. Binding pattern of clear cell carcinomas was similar to gestational endometrium, with PNA and UEA-1 showing strong affinity. This pattern is in contrast to clear cell carcinomas of the kidney, that do not bind PNA and UEA-1. Mucinous cystadenomas exhibited binding patterns identical with cervical epithelium. Malignant counterparts of the described tumors were characterized by the partial loss of lectin binding and uneven distribution of the binding reaction.

Common epithelial ovarian tumors. Immunohistochemical intermediate filament profiles

The authors studied 79 common epithelial ovarian tumors in order to ascertain the intermediate filament profiles in formalin-fixed and methacarn-fixed, paraffin-embedded surgical pathology materials. Ultra-structural correlations were attempted with several tumors. All categories of common benign and malignant epithelial tumors were examined. Antibodies used in the study included antikeratins (AE1/AE3, 35BH11, 34BE12), carcinoembryonic antigen (CEA), and vimentin. All ovarian epithelial tumors expressed keratin in uniform fashion, except high molecular weight keratin (34BE12) which was focal. Vimentin was coexpressed with cytokeratins in 42% of serous carcinomas, 71% of endometrioid carcinomas, and 7% of clear cell carcinomas. Vimentin decoration in serous carcinoma was very focal, whereas endometrioid decoration tended to involve larger areas, similar to uterine-based endometrial adenocarcinoma. Mucinous, Brenner, and solid (not otherwise specified) ovarian tumors were positive only for cytokeratin. Carcinoembryonic antigen luminal staining was present in 52% of serous carcinomas and 87% of mucinous carcinomas. Whereas there are distinct differences in intermediate filament expression among ovarian carcinomas, these differences do not allow for specific categorization of ovarian neoplasms because there is some overlap of intermediate filament expression. In order to differentiate ovarian carcinoma from other carcinomas and mesothelioma, other methods of study would be necessary in addition to intermediate filament profiles, such as CEA immunohistochemistry, mucin histochemistry, and ultrastructural study.

Ovarian Mucinous Cystadenocarcinoma Producing α-Fetoprotein

Common epithelial ovarian tumors associated with alpha-fetoprotein (AFP) production are rare. A case of ovarian mucinous cystadenocarcinoma producing both AFP and carcinoembryonic antigen (CEA) is presented. A 53-year-old postmenopausal woman with right adnexal tumor underwent total hysterectomy and right salpingo-oophorectomy. Preoperative serum CEA and AFP levels were elevated to 660 and 1,120 ng/ml, respectively, and both decreased to their normal ranges after surgery. Histologically, the right ovarian tumor was diagnosed as a mucinous cystadenocarcinoma, composed of both intestinal-type cells and endocervical-type cells. Intestinal-type cells were identified ultrastructurally, with cells resembling neuroendocrine cells as well as gobletlike cells with many mucinous granules. Yolk sac or teratomatous components were not identified. By the immunoperoxidase technique, CEA was positive in well to moderately differentiated mucinous cells lining lumina, whereas AFP-positive cells were intermingled with CEA-positive cells in moderately differentiated epithelia.

Immunohistochemical demonstration of CA 125, CA 19-9 and CEA in normal and pathologically changed adnexa

Sections of formalin fixed and paraffin embedded tissue samples from 11 normal ovaries and fallopian tubes, 13 tuboovarian abscesses, 3 carcinomas of the fallopian tube and 105 common epithelial ovarian tumors were examined to demonstrate the morphological background of elevated serum levels of CA 125, CA 19-9 and CEA. 9/13 tuboovarian abscesses were positive for CA 125 and 5/13 for CA 19-9, elevated serum levels of these markers could be explained by the expression of markers in epithelial cells of the inflamed tubes. Serous tumors and undifferentiated carcinomas were CA 125 positive in 86% and 70%, respectively. All mucinous tumors were CA 125 negative; most of them, however, were CA 19-9 positive (77%). CEA was found in endometroid tumors in 44% of the cases. Only one marker was detected in 42% of the borderline tumors and carcinomas. The immunohistochemical detection of a marker indicates its potential usefulness for monitoring. Although we used three tumor markers, 7% of the ovarian malignancies were negative for all markers tested. The marker expression was very heterogeneous: positive areas were directly adjacent to negative areas. There was no specificity for histological type, tumor localization or malignancy, all markers could be detected in some of the benign tumors, CA 125 and CA 19-9 also in inflamed tissue.