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5542 Background: Detection of cancer with improved discrimination compared to current blood tests could be achieved using an approach that assesses extracellular vesicles (EVs). This approach should have high sensitivity (se) because of EVs abundance in blood and high specificity (sp) by assaying EVs with multiple cancer-related protein and glycosylation epitopes (PGEs) co-localized on their surfaces. We are developing a platform technology that detects multiple cancer-related PGEs co-localized on the same EV using immunoaffinity-capture and proximity-ligation qPCR. In this study, we compare the performance of this technology vs plasma CA125 for correctly categorizing early-stage high-grade serous ovarian cancer (HGSOC) vs healthy/benign ovarian tumors (OT). Methods: We evaluated our EV-based platform technology using 7 PGE combinations to discriminate HGSOC from benign adnexal masses. We first derived a prediction model on a retrospectively collected cohort of 42 HGSOC and 26 benign OT samples from 2 commercial vendors and 24 healthy controls (HC) using a machine-learning algorithm. We validated this model on an independent cohort [89 HGSOC: Stage I (17), II (35), III (37); 192 benign OT] from university-associated biobanks and 124 HC. We also assessed the assay’s performance in plasma from 87 women with off-target cancers and 42 women with inflammatory conditions from commercial vendors. For each sample, we also measured CA125 levels using a commercial ELISA. Results: The prediction model distinguishes HGSOC from benign and HC with an AUC of 0.965 (95% CI 0.93-0.99), with 89.9% (0.82-0.95) se at 98% sp. For stage I/II HGSOC, the model achieves an AUC of 0.942 (0.9-0.99), with 84.6% (0.72-0.93) se at 98% sp. By comparison, CA125 achieves an AUC of 0.875 (0.81-0.94) and 44.2% (0.3-0.59) se at 98% sp. Direct comparison of CA125 and our model shows a significant difference at 98% sp for both all and stage I/II HGSOC (McNemar p-val < 0.001). When comparing HGSOC to HC, there is no significant difference between our model and CA125 (p-val = 1.0). There is a significant difference when comparing patients with all stage and stage I/II HGSOC to patients with benign OT (p-val < 0.001). Our assay had 1 false positive and CA125 had 3 false positives out of 42 inflammatory cases. Conclusions: These preliminary data suggest our platform technology for detecting PGEs co-localized on individual EVs may detect all stages of HGSOC from plasma with high se at a very high sp. Our assay may improve on CA125 by distinguishing stage I/II HGSOC from benign OT and could have clinical utility for both early detection and surgical referral recommendation for benign and malignant OT. While the diverse cohorts in this study may present challenges in interpretation, the reproducibility in an independent cohort is encouraging and supports further investigation using cases and controls from well-defined cohort studies.

The hypothesis on the pathogenesis of epithelial ovarian cancer continues to evolve. Although epithelial ovarian cancer had been assumed to arise from the coelomic epithelium of the ovarian surface, it is now becoming clearer that the majority of serous carcinomas arise from epithelium of the distal fallopian tube, whereas clear cell and endometrioid cancers arise from endometriosis. Molecular and genomic characteristics of epithelial ovarian cancer have been extensively investigated. Our understanding of pathogenesis of the various histologic types of ovarian cancer have begun to inform changes to the strategies for management of epithelial ovarian cancer, which represent a paradigm shift not only for treatment but also for prevention, which previously had not been considered achievable. In this article, we will discuss novel attempts at the prevention of high-grade serous ovarian cancer and treatment strategies for two distinct entities in epithelial ovarian cancer: low-grade serous and clear cell ovarian carcinomas, which are relatively rare and resistant to conventional chemotherapy.

e17122 Background: Mismatch repair (MMR) deficiency is observed in 25-30% of all endometrial cancers. This can be detected by the absence of MMR protein staining on immunohistochemistry (IHC), and is used in many jurisdictions as a screen for an inherited mutation in one of the MMR genes (Lynch Syndrome). Only 10% of women with MMR deficiency (MMRd) have Lynch syndrome, but MMRd may still have prognostic significance. The objective of this study was to compare clinical outcomes between MMR deficient and proficient low-risk endometrioid endometrial cancers (stage IA, grade 1/2). Methods: This was a retrospective population-based cohort study of all low-risk endometrial cancers from Vancouver Coastal Health authority region from 2011 to 2016 that were assessed for MMR deficiency (MMRd). Primary outcome measures were recurrence rates expressed per person-years (py), progression free survival (PFS) and overall survival (OS) calculated using Kaplan-Meier method and log-rank tests. Cox proportional hazards model estimated the association between MMRd and recurrence and death after adjustment for covariates, expressed as hazard ratios (HR). Results: There were 475 low-risk patients, including 131 MMRd (27.6%) and 345 MMRp (proficient) patients. Women with MMRd tumors had higher recurrence rates (3.53p100py vs 1.21p100py) and worse PFS (p = 0.0082) compared to women with MMRp tumors. After adjustment for age, LVSI status, adjuvant therapy, and post-operative grade, MMRd status remained associated with a higher risk of recurrence (HR 2.99, 95% CI 1.27-7.04). There was no significant difference in OS between MMR groups (HR 1.38, 95% CI 0.57-3.33). Conclusions: In low-risk stage IA grade 1 or 2 endometrioid endometrial cancers, MMR deficiency is associated with a higher recurrence rate than in MMR proficient cases, after adjustment for covariates, implying that MMR deficiency reflects a different biology in endometrial cancer.

5586 Background: Adjuvant radiotherapy improves progression-free survival in intermediate and high-risk endometrial cancer. However, so far there is no evidence of improved overall or disease-specific survival after adjuvant radiotherapy. There is accumulating evidence that MMR proteins are involved in DNA repair following radiotherapy. We investigated the predictive value of MMR status in terms of survival benefit after adjuvant radiotherapy in patients with stage IB/II, grade 3 endometrioid endometrial cancer (EEC). Methods: A retrospective multicenter cohort study was performed to compare patients with histopathologically confirmed stage IB/II grade 3 EEC with and without adjuvant radiotherapy. Patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identifying ECs as either MMR-deficient, POLE, p53abn or p53wt. Multivariable Cox regression analysis explored associations between patient characteristics, adjuvant treatment and outcome. Results: A total of 128 patients were analyzed, including 57 patients (43.0%) with MMR-deficient EECs. Baseline characteristics were comparable, except a higher proportion of MMR-deficient EECs were stage II (36.8% vs. 15.5%, p = 0.006). Eighty-two patients (64.1%) received adjuvant radiotherapy (external beam [n = 55], vaginal brachytherapy [n = 27]). In multivariate analysis, adjuvant radiotherapy was independently associated with improved disease-specific survival in patients with MMR-deficient EECs (hazard ratio 0.19, 95%-CI 0.05 - 0.77), but not in patients with MMR-proficient EECs (hazard ratio 0.92, 95%-CI 0.37 - 2.31). Conclusions: Adjuvant radiotherapy improved disease-specific survival in patients with MMR-deficient EECs, but not in those with MMR-proficient EECs. This study demonstrates the predictive ability of MMR IHC to identify women who likely have increased benefit from radiotherapy.

5518Background: Classification of endometrial carcinomas (ECs) by morphologic features is inconsistent, and yields limited prognostic and predictive information. A new system for classification bas...

5543 Background: CD8 positive intra-epithelial tumor infiltrating T cells (TIL) are associated with improved outcomes in ovarian cancer, particularly in HGSC. Radiotherapy (XRT) has immunologic eff...

5023 Objective: UPSC is an aggressive type of endometrial cancer characterized by a high recurrence rate and a poor prognosis. Prior studies evaluating treatment of UPSC are limited by small numbers of patients and inclusion of unstaged patients. The purpose of this study is to evaluate the efficacy of adjuvant chemoradiation (defined as concomitant vaginal cuff radiation and platinum-based chemotherapy) in a large cohort of stage I UPSC patients. Methods: We identified 182 patients with UPSC who underwent complete surgical staging between 1987–2003. Differences in disease free survival (DFS) and overall survival (OS) were determined by Kaplan-Meier log rank method. Results: 74 of the182 cases were FIGO stage I: 33 stage IA, 29 stage IB and 12 stage IC. Stage IA patients were further divided into 2 groups: patients with no cancer in the hysterectomy specimen (defined as no residual uterine disease, n=12) and patients with residual uterine disease (n=21). Stage IA patients with no residual uterine disease ...

6702 Background: The manifestation of lymphoma as a pelvic mass is rare with most previous literature reporting a poor prognosis. Our objective is to report our experience with this rare gynecologic malignancy. Methods: Retrospective review was performed on patients (pts) diagnosed with lymphoma of the gynecologic organs between 1980 and 2004. Medical records, diagnostic imaging and pathology reports were reviewed. Histologic classification was based on the Working Formulation and staging on the Ann Arbor system. Results: 19 pts with diagnosis of pelvic lymphoma (PL) were identified. 18 of these presented as primary lymphomas of gynecologic organs. Location of pelvic mass included ovarian (11), uterine (2), vaginal (2), uterine and ovarian (1), vaginal and cervical (1). The median age at presentation was 53 yrs (19–87). Eleven percent presented as stage I, 5% stage II, 5% stage III, and 79% stage IV. Presentations included abdominal and pelvic discomfort and bloating (32%), abnormal vaginal bleeding (11%)...