Abstract

Abstract Background: Uterine Papillary Serous Carcinoma (UPSC) comprises 5-10% of all endometrial cancers but is responsible for nearly 40% of all endometrial cancer-related deaths. Progression-free survival (PFS) controlled for stage is also markedly shorter in UPSC compared to Type 1 endometrial cancers. Unlike endometrioid carcinoma, in which depth of myometrial invasion, grade, and lymphovascular space invasion (LVSI) are risk factors for extrauterine spread, UPSC often metastasizes in those with no myometrial invasion. Objective: The objective of this study is to identify markers that may predict metastatic disease in women with non-invasive UPSC or portend a shorter progression free survival. Materials: A retrospective chart review was performed on women diagnosed with Stage IA or Stage III/IV UPSC without myometrial invasion from 1995-2008. Examined factors include age, parity, race, weight, LVSI, CA125 levels, and tumor location within the endometrium. Tissue microarrays (TMAs) were constructed using paraffin blocked specimens and stained for ER, PR, p53, VEGF, Claudin 3, Claudin 4, Her-2/neu, Her-3, Synuclein gamma, and Maspin. Chi-square analysis, Student's t-test, and Fisher's Exact analysis were used where appropriate to detect statistically significant differences in these 2 groups with Kaplan-Meyer analysis used to determine PFS. Significance was represented at p<0.05. Results: Thirty-two patients were identified to have UPSC without myometrial invasion, 24 (75%) comprising Stage IA and 8 (25%) having Stage III/IV disease. Pathology blocks were available for 21 patients (14 Stage I and 7 Stage III/IV). CA125 was the only factor to achieve significance (p=0.04) in predicting metastatic spread; biomarkers, either alone or in combination, were not predictive of metastatic disease. In Stage I disease, positive ER status was associated with a significantly longer PFS (p<0.001) while in Stage III/IV disease, positive Her-3 status was associated with a shorter PFS (p=0.014). Conclusions: In addition to traditional risk factors not being predictive of metastatic disease, molecular markers that have been associated with metastatic disease and a worsening prognosis do not appear to be predictive in UPSC. However, the contribution of ER status and Her-3 needs to be further evaluated as this may offer new insight into therapeutic options for treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5175. doi:10.1158/1538-7445.AM2011-5175

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