Abstract 1137: Racial differences in oncogene mutations detected in endometrial cancers

Endometrial cancer is the most common gynecologic cancer, with an estimated 42,000 new cases in 2010. Histologic types of endometrial cancer and stage at diagnosis differ substantially between African Americans (AA) and whites, but AA women experience poorer survival even after accounting for these factors. Additionally, other research suggests this disparity persists after controlling for co-morbid conditions, access to care, and treatment decisions. We hypothesize that there are differences in the molecular biology of tumors from white and AA women, beyond histologic type and grade, which may lead to the increased risk of death seen in AA women after an endometrial cancer diagnosis. After IRB approval, we performed a case-only retrospective analysis of patients with endometrial cancer, for whom we had tumor blocks, diagnosed from 1990-2005 at a single institution. Demographic and clinical variables were obtained from medical record review. Tumor histologic type, stage, and grade were obtained from the Metropolitan Detroit Cancer Surveillance System, part of the SEER program. Tumor histologic type and grade were confirmed by a gynecologic pathologist by slide review. We selected 150 archived tumors, including all high grade cases of any race (35 white, 40 AA), all low grade, endometroid tumors from AA women (n=44), and 31 low grade tumors from white women. Tumor DNA was extracted from formalin fixed paraffin embedded tissue using standard methods. We examined 238 mutations in 19 common oncogenes using the OncoCarta Assay v1.0 (Sequenom). Chi-square tests and Fisher's exact tests were used to assess differences in distribution of clinical and demographic variables by race or oncogene mutation status. We identified 20 mutations in 2 oncogenes in tumors from 19 women (12.7%). The most common mutation was in PIK3CA, the gene coding for the catalytic subunit p110α of PI3K, representing 15/20 (75%) of detected mutations. In PIK3CA, the following mutations were identified: R88Q in the p85-binding domain, E542K, M1043I and P539R in the helical domain, and H1047R in the kinase domain. Previous data suggest these mutations induce a gain of PI3K function and prognosis may vary by location. An additional 4 samples had activating mutations in KRAS (1 G12D, 1 G12V and 2 Q61H). No other mutations were identified. 13% of endometroid tumors harbored mutations, (11 PIK3CA and 2 KRAS). Among tumors from women with low grade endometroid cancers, race was significantly associated with harboring a mutation (p=0.04), with all 7 PIK3CA mutations were identified in AA women. All 4 KRAS mutations were found in AA women (p=0.13). This study provides preliminary evidence that the underlying molecular biology of some subtypes of histologically similar endometrial cancers differ by race. 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 1137. doi:10.1158/1538-7445.AM2011-1137