Purpose: The tumor suppressor PTEN gene and the PIK3CA oncogene are frequently mutated in uterine endometrioid carcinoma (UEC). PTEN mutations are also common in complex atypical hyperplasia (CAH), the precursor lesion of UEC. The status of PIK3CA has not yet been explored in CAH. In this study, we evaluated both CAH and UEC for PTEN and PIK3CA mutations. Experimental Design: Neoplastic tissue was microdissected, and DNA was extracted from 29 cases of CAH. DNA was available from 44 UEC cases previously characterized for PTEN mutations. Direct DNA sequencing of exons 9 and 20 of the PIK3CA gene was done on all 73 cases. In addition, CAH cases were analyzed for PTEN mutations. Statistical analyses were done using the Fisher's exact test. Results: Two (7%) of 29 CAH and 17 (39%) of 44 UEC cases contained a PIK3CA mutation (P = 0.003). Fourteen (48%) of 29 CAH cases had a PTEN mutation, but none contained both a PTEN and PIK3CA mutation. Twenty-five (57%) of 44 UEC cases had a PTEN mutation, and 12 (48 %) of these 25 cases also contained a PIK3CA mutation. Coexistent PIK3CA and PTEN mutations were significantly correlated with UEC compared with CAH (P = 0.002), but the association in UEC did not reach statistical significance (P = 0.21). Conclusions: PIK3CA is the most commonly mutated oncogene in UEC; however, mutations are uncommon in CAH. Thus, mutations in PIK3CA, unlike PTEN mutations, are associated with invasion.These findings suggest that mutations in PIK3CA may serve as a marker of invasion with potential clinical use. Furthermore, PIK3CA and PTEN mutations may play distinct roles in endometrial tumorigenesis.Within the last 10 years, our knowledge of the molecular genetics of endometrial cancer has expanded with the discovery of mutations in genes, such as PTEN, K-RAS, CTNNB1, and TP53. These discoveries have led to a better understanding of the pathogenesis of endometrial cancer and its distinct histologic subtypes, broadly categorized as type I and II cancers, which are thought to arise via different pathogenetic pathways. Uterine endometrioid carcinoma (UEC) is the most common histologic subtype, representing >85% of cases. Not only is PTEN the most commonly mutated gene in UEC, the mutations also occur early in its pathogenesis as they are present at approximately the same frequency in complex atypical hyperplasias (CAH), the precursor lesion of UEC (1, 2).Recently, mutations of a novel oncogene (PIK3CA) were discovered in multiple human epithelial cancers, including UEC (3, 4). PIK3CA encodes the catalytic p110-a subunit of phosphatidylinositol 3-kinase (PI3K), a lipid kinase that generates phosphatidyl inositol-3,4,5-triphosphate by phosphorylating phosphatidyl inositol-3,4-diphosphate. This in turn activates the AKT/mammalian target of rapamycin oncogenic pathway, directly opposing the actions of the lipid phosphatase PTEN (5). It is unclear what role mutations in PIK3CA play during endometrial tumorigenesis and what, if any, additional role they confer over PTEN mutations. Recent literatur...

OBJECTIVE To examine whether treatment with guideline-recommended care (surgery and chemotherapy) is associated with mortality differences between black and white women with advanced epithelial ovarian cancer. METHODS We conducted an observational cohort study using the Surveillance, Epidemiology, and End Results (SEER) linked to Medicare claims for 1995-2007. We evaluated long-term survival for 4,695 black and white women with stage III or IV epithelial ovarian cancer with Kaplan-Meier analysis and Cox regression, and then in patients matched by propensity score to create two similar cohorts for comparison. We investigated the association between race, stage, and survival among women who were treated with guideline-recommended care and those who received incomplete treatment. RESULTS Black women with advanced epithelial ovarian cancer were more likely to die than white women; unadjusted hazard ratio (HR):1.27 (95% confidence interval [CI]: 1.10-1.46). Black women were less likely than white women to receive guideline-recommended care (54% vs. 68%, p<0.001) and women who did not receive recommended treatment had lower survival than women who received recommended care. Cox proportional hazards models demonstrated no black versus white differences in mortality among women who were treated with guideline-recommended care; adjusted HR:1.04 (95% CI: 0.85-1.26) or among women who received incomplete treatment; adjusted HR:1.09 (95% CI: 0.89-1.34). The survival analysis of patients matched by propensity score confirmed these analyses. Conclusions Differences in rates of treatment with guideline-recommended care are associated with black–white mortality disparities among women with advanced epithelial ovarian cancer.