PTEN mutation located only outside exons 5, 6, and 7 is an independent predictor of favorable survival in endometrial carcinomas

Although the prognostic impact of PTEN mutation in endometrial carcinoma is beginning to be analyzed, the prognostic significance of mutated PTEN exon s has not ever been described. Sixty-seven endometrial carcinomas were analyzed for PTEN mutations using s ingle-strand conformation polymorphism analysis and DNA sequencing. First, survival rates were compared according to PTEN status and mutated PTEN exon s. Subsequently, univariate and multivariate analyses of various favorable prognostic factors for survival were conducted. The associations between PT EN mutation and clinicopathological features were also statistically evalua ted. PTEN mutations were detected in 37 of 67 (55%) specimens. Among 47 mutation s, frameshifts (57%) and mutations in exon 8 (38%) were most frequent. In u nivariate analysis, a factor of PTEN mutation only outside exons 5-7 was as sociated with significantly better survival (P = 0.02), although mutation i n any exon of PTEN was not (P = 0.33). Subsequent multivariate analysis rev ealed that factors of mutation only outside exons 5-7 of PTEN, stage I/II, and G(1) were significant and independent prognostic indicators for favorab le survival (P = 0.004, 0.004, and 0.0006, respectively). In the subset of advanced-stage disease, mutation only outside exons 5-7 was associated with a trend toward better survival (P = 0.13). No significant correlation was observed between PTEN mutation and estrogen-related clinicopathological fea tures. In conclusion, we find that PTEN mutation located only outside exons 5-7 is a significant and independent positive prognostic indicator for survival. The current observation has prognostic and therapeutic implications for the management of patients with endometrial carcinoma.