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Ovarian cancer is a major cause of lethality from gynecological malignancies, and there is a lack of reliable and specific serum markers for this disease. Eicosanoid-related enzymes have previously been implicated in the pathogenesis of various types of cancer, but little is known about the relevance of lipoxygenase isoforms in ovarian cancer and the results on cyclooxygenases are conflicting. For this study, we quantified the expression of eicosanoid-related enzymes (cyclooxygenase-1 and cyclooxygenase-2, 15-lipoxygenase-1 and lipoxygenase-2, 5-lipoxygenase) in normal and malignant human ovarian tissue by real-time polymerase chain reaction and found a 22-fold elevated expression of 15-lipoxygenase-2 in malignant specimens when compared with normal ovarian tissue (P=0.001). In ovarian carcinoma metastases, expression of the enzyme was also augmented (20-fold upregulation, P=0.004). For 15-lipoxygenase-1 and cyclooxygenase-2, we did not observe differential expression, but there was a trend for increased steady-state concentrations of cyclooxygenase-1 (P=0.1 for ovarian carcinoma, P=0.011 for metastases) and 5-lipoxygenase (P=0.1 for ovarian carcinoma, P=0.018 for metastases, respectively). These data indicate that expression of 15-lipoxygenase-2 mRNA is strongly augmented during ovarian carcinogenesis and that the enzyme may constitute a suitable candidate as a tumor marker.

The immunohistochemical expression of 72-kDa type IV collagenase [matrix-metalloproteinase (MMP)-21], basement membrane component type IV collagen and proliferation-related antigen Ki 67 were investigated in 43 benign, borderline, and malignant serous tumors of the ovary. The results were compared with the histotypes of ovarian serous tumors and with their clinical behavior. Serum evaluation of MMP-2 was performed in 14 patients with cystadenocarcinoma and the data compared with that of a control group. The basement membrane (BM) was continuous in benign cystadenomas and in some borderline tumors, whereas it was discontinuous or absent in other borderline tumors, in borderline tumors with microinvasion, and cystadenocarcinomas. The percentage of MMP-2- and Ki 67-expressing cells increased from cystadenomas to borderline tumors, being the highest in malignant tumors; a frequent basal disposition of the MMP-2 cytoplasmic granules also was observed in cystadenocarcinomas. Statistical analysis demonstrated that MMP-2 expression was inversely related to BM integrity. Serum MMP-2 values did not differ from that of the control group. Cox regression analysis showed that tumor stage and grade were significant prognostic factors, whereas MMP-2 and Ki 67 immunohistochemical expression added no further significant information to the prognosis. The investigators conclude that the correlation between increasing MMP-2 expression and BM alteration gives support to the hypothesis of a direct role of the metalloproteinase in the process of destructive stromal invasion. MMP-2, type IV collagen, and Ki 67 immunodetection varied according to the histologic classification of ovarian serous tumors. However, neither these factors nor the serum evaluation of MMP-2 appear useful as prognostic predictors in this series.

We performed flow cytometry and AgNOR counts on 117 serous and mucinous ovarian tumours, comprising 56 cystadenomas, 21 borderline tumours, and 40 cystadenocarcinomas. DNA aneuploidy was present in one cystadenoma and in 11% of mucinous and 46% of serous cystadenocarcinomas. All borderline tumours were DNA diploid. Major and minor FIGO stages and flow cytometrically determined DNA ploidy and DNA index were prognostically significant. Age, histological type (serous versus mucinous), flow cytometric proliferative index, and AgNOR counts were not predictive of survival. Cystadenomas and borderline tumours had lower rates of proliferation than cystadenocarcinomas. AgNORs correlated with DNA ploidy and proliferative index. Borderline tumours showed elevated AgNOR numbers despite low proliferative indices and universal DNA diploidy, suggesting that AgNOR numbers may be related to nuclear events other than proliferation and DNA ploidy.

We studied the expression of cytoskeletal intermediate filaments in different types of ovarian and uterine sarcomas and carcinomas. In both uterine and ovarian leiomyosarcomas, in endometrial stromal sarcomas, and also in ovarian sarcomas, most tumor cells appeared to be positive for desmin, the muscle type of intermediate filament protein. In most of the tumors, vimentin was present only in some neoplastic cells and in the vascular endothelia. Interestingly, both uterine and ovarian malignant mixed mesodermal tumors appeared to express several types of intermediate filaments, most of the stromal cells being positive for vimentin or desmin, and the epithelial component expressing keratin. The results show that most of the sarcomatous tumors of the ovary and uterus express mainly muscle type of intermediate filament protein. The results also demonstrate the ability of cells of mesodermal origin to express epithelial cytoskeleton markers--cytokeratins.

Polyclonal antibodies to cytokeratins, vimentin, and desmin and monoclonal antibodies to vimentin and to individual cytokeratin polypeptides, specific for glandular epithelia (RGE 53) or kertinizing stratified squamous epithelia (RKSE 60), have been applied in gynecological tumors with simple or complex composition. In general, tumors with simple composition showed reaction patterns fitting their known epithelial or mesenchymal nature, i.e., cytokeratin positivity in epithelial tumors only, vimentin positivity in mesenchymal tumors, and expression of desmin and vimentin in muscle cell tumors. Rather frequently, coexpression of cytokeratins and vimentin was noted in endometrial adenocarcinomas. Tumors with complex composition, such as müllerian mesodermal mixed tumors (MMMTs), that may pose considerable problems in conventional histopathology revealed various reaction patterns, with either expression of only cytokeratins or coexpression of cytokeratins and vimentin in carcinomatous areas and expression of only vimentin in sarcomatous areas. However, in addition, some MMMTs contained cells that were also positive for desmin. Intermediate filament protein immunohistochemistry appeared to be helpful in establishing a diagnosis of MMMT and in characterizing the different tumor components, which may prove to be useful in the evaluation of gynecological treatment protocols.

Peripheral and ovarian venous concentrations of testosterone, androstenedione, estradiol-17 beta, and estrone were measured in 30 postmenopausal women. Ovarian venous concentrations of testosterone and estradiol-17 beta were 5.6 and 4.3 times the peripheral concentrations of women with normal ovaries. This suggests that the ovaries of postmenopausal women continue to secrete these two steroids. Mean peripheral testosterone concentrations in 14 postmenopausal women with a nonfunctional or functional ovarian tumor were increased significantly. Ovarian venous concentrations of these four steroids from the side draining the tumor-bearing ovary were increased in 40 to 80% of the women. The venous concentrations from the normal ovary were also increased in 22% or more of the women with an ovarian tumor. Any ovarian neoplasm in postmenopausal women may be associated with increased ovarian sex-steroid secretion.

An examination of the biokinetics and biodistribution of i.p. administered 131I- or 111In-labelled 791T/36 antibody (1 mg) has been carried out in five patients with stage III/IV ovarian cancer. Blood kinetics and urinary excretion of the radiolabels were assayed. Scintigraphy was performed immediately following administration and before and after peritoneal lavage at 48 h. Blood levels of both preparations rose over the first 20-40 h reaching 8-14% of the administered dose in the circulation and then declined (T1/2 of 40 h). Circulating radiolabel was still attached partially to antibody as shown by precipitation with anti-mouse IgG antiserum. The rapid appearance of radiolabel in the bloodstream meant that any tumour localization could be from circulating antibody rather than local infiltration. Interpretation of the images was difficult and the distribution of the tracer was different from that previously observed using i.v. administration of antibody. In some cases the images were confusing and the uptake of activity did not fit in with the clinical knowledge of the disease or the findings from laparoscopy. Tumour specimens resected at 4-5 days showed up to 0.02% of the dose g-1.

Mucinous tumors of the ovary are incidentally associated with ovarian sarcoma. Several cases of sarcoma-like mural nodules in ovarian mucinous tumors have been described previously, but only two well-documented cases of true sarcoma were reported. The purpose of this article is to report a case of sarcoma occurring in ovarian mucinous neoplasm, which differs histologically from the two cases described earlier. This case is the first of its kind with immunohistochemical characterization.