PTEN methylation is associated with advanced stage and microsatellite instability in endometrial carcinoma

Loss of heterozygosity and mutations in the PTEN (MMACI) tumor suppressor g ene are frequent in endometrial carcinoma. Promoter hypermethylation has re cently been identified as an alternative mechanism of tumor suppressor gene inactivation in cancer, but its importance in the PTEN gene in endometrial carcinoma is unknown. The purpose of our study was to assess the frequency of promoter methylation of the PTEN gene and to determine its correlation with clinicopathologic variables in a prospective and population-based seri es of endometrial carcinomas with complete follow-up. Presence of PTEN prom oter methylation was seen in 26 of 138 patients(19%). Methylation was signi ficantly associated with metastatic disease (p = 0.01) and a microsatellite unstable phenotype (p = 0.006), In conclusion, we find that PTEN promoter methylation is relatively frequent in endometrial carcinoma, Its associatio n with metastatic disease and microsatellite instability implicates its imp ortance in the development of this tumor type, (C) 2001 Wiley-Liss, Inc.