Endocrine biomarkers in low-grade serous ovarian cancers (LGSC) and serous ovarian tumors of low malignant potential (LMP).

e18045 Background: LGSC and serous ovarian LMP tumors are rare entities along a disease continuum. Because they are relatively chemotherapy resistant, there is interest in targeted treatment, including endocrine therapy. In studies of endocrine agents for treatment of recurrent ovarian cancer, tumor estrogen receptor (ER) status alone does not effectively predict outcomes. The objective of this study is to utilize protein and gene expression from ER and downstream targets to identify signaling components that will act as prognostic and predictive biomarkers. Methods: A single institution tumor registry was queried for patients with LGSC or serous LMP tumors between 1993-2016. Formalin-fixed, paraffin embedded (FFPE) tissue was obtained. Clinicopathologic data was collected. Immunohistochemistry (IHC) was performed and scored as dichotomous (+/-) and continuous (H-score). NanoString nCounter platform was used for gene expression of a predesigned endocrine biomarker panel. Wilcoxon Rank Sum was used to compare mRNA and protein expression. Survival analyses were performed using Cox proportional hazard (PH) method with elastic net to fit the prediction model for the gene panel. Results: Tissue was analyzed from 23 LGSC, 71 serous LMP tumors, and 2 recurrences. At diagnosis, 86% of patients with LMP tumors had stage I disease vs 78% of patients with LGSC had stage III/IV disease. There were 7 (10%) LMP and 13 (56.5%) LGSC recurrences. Median initial PFS was 76 and 37 months and median OS was 88 and 82 months for LMP and LGSC, respectively. Fourteen received endocrine therapy; nine for treatment of recurrent LGSC. Median therapy was 21 months, with 3 complete responses, 2 partial responses and 1 stable disease. All tumors were ER+ (median H-score 210) and 89% were PR+ (median H-score 130). ER H-scores and ESR1 expression levels were not significantly different between LGSC and LMP tumors (p = 0.1942, p = 0.0893). PR H-scores were higher in LMP tumors (p < 0.00001) but PGR expression was not significantly different (p = 0.6581). In the Cox PH analysis, ER H-score was a significant predictor of both PFS and OS (p < 0.001, p = 0.004). The Cox model identified independent sets of gene expression associated with PFS and OS in both the LGSC and LMP cohorts (c-indices 0.679, 0.570, 0.626, 0.689). Conclusions: Endocrine therapy is an active area of interest in the treatment of ovarian neoplasms. ER H-score and gene expression of downstream ER targets could improve upon the use of hormone receptors to determine risk of recurrence and guide use of adjuvant endocrine therapy.

The Ep-CAM: A potential candidate for diagnosis in ovarian cancer

e16571 Background: The purpose of this study was to examine the expression of splice variants of the Ep-CAM gene in normal ovarian epithelial tissue and ovarian carcinoma and further to associate the expression of Ep-CAM with clinicopathologic characteristics if such an association exists. Methods: Ep-CAM expression was examined by semiquantitative PCR in 122 ovarian tumors (92 adenocarcinomas, 10 low malignant potential (LMP) tumors, and 10 adenomas) and 10 normal ovaries. Results: In carcinomas as well as LMP tumors and adenomas, Ep-CAM mRNA expression was significantly elevated compared to that in normal ovary samples. Ep-CAM mRNA expression level in carcinomas was significantly elevated compared to that in adenomas and Ep-CAM mRNA expression level in advanced clinical stage diseases was significantly higher than that in early stage diseases in ovarian carcinomas. With regard to histological type, Ep-CAM mRNA expression level in mucinous adenocarcinomas was significantly higher than those in the other tissue subtypes. Conclusions: These features imply that Ep-CAM expression may play an important role in ovarian cancer development and progression, and this may be useful as a diagnostic marker. No significant financial relationships to disclose.

Preoperative Serum Tissue Factor Levels Are an Independent Prognostic Factor in Patients With Ovarian Carcinoma

Purpose Tissue factor (TF) is a procoagulant that plays an important part in tumor angiogenesis. We sought to determine the role of preoperative serum TF levels in predicting clinical outcome in patients with ovarian cancer. Materials and Methods TF expression was determined by reverse transcriptase polymerase chain reaction in ovarian cell lines. Using enzyme-linked immunosorbent assay, we assessed preoperative serum TF levels in 98 women with invasive epithelial ovarian carcinoma, 30 with low malignant potential (LMP) tumors, 16 with benign tumors, and a separate validation group of 39 women with adnexal masses. Clinical information was gathered from chart review. Results TF was expressed in four of the five ovarian cancer cell lines, but absent in the nontransformed cells. Ovarian cancer patients had a median preoperative serum TF level of 85.2 pg/mL, which was significantly higher than in those with LMP tumors (12.8 pg/mL; P < .01) and benign adnexal disease (30.7 pg/mL; P < .01). TF ≥ 190 pg/mL was significantly associated with decreased patient survival (P < .01). After adjusting for other clinical variables in a multivariate Cox regression model, TF ≥ 190 pg/mL was an independent prognostic factor (P < .01). Analysis of serum TF levels from the validation set confirmed that high TF (≥190 pg/mL) was associated with a 3.4-fold increase in risk of death from disease (P = .02) and shorter survival (P = .01). Conclusion Preoperative serum TF levels are significantly elevated in patients with ovarian carcinoma. Elevated preoperative TF level is an independent prognostic factor for death from disease.

Preliminary analysis of the behavior of stage I ovarian serous tumors of low malignant potential: a Gynecologic Oncology Group study.

PURPOSE From December 1983 through February 1992, a prospective study designed to determine the clinical course of patients with ovarian tumors of low malignant potential (LMP) was conducted by the Gynecologic Oncology Group (GOG). MATERIALS AND METHODS This protocol was developed to evaluate the following (1) the biologic behavior of ovarian LMP tumors, (2) the effectiveness of melphalan chemotherapy in patients with clinically detectable residual disease after surgical staging and in patients whose tumors progress or recur after surgical therapy, and (3) the response rate to cisplatin in those who failed to respond to melphalan therapy. The study group consisted of 146 assessable patients with stage I serous LMP tumors. All of these women had the affected ovary (or ovaries) removed, and a complete staging operation was performed in each case. While 123 patients had a total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO), 21 retained the uterus and one normal-appearing ovary and fallopian tube. No adjuvant chemotherapy or radiation therapy was administered to any patients in the stage I study group. RESULTS The median follow-up time was 42.4 months (range, 1.6 to 108). Thus far, no patient with a stage I ovarian serous LMP tumor has developed recurrent disease. CONCLUSION Stage I ovarian serous LMP tumors rarely, if ever, recur. Limited resection, after meticulous surgical exploration, is adequate therapy for women of reproductive age.