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PTEN Mutation Located Only Outside Exons 5, 6, and 7 Is an Independent Predictor of Favorable Survival in Endometrial Carcinomas

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan

Although the prognostic impact of PTEN mutation in endometrial carcinoma is beginning to be analyzed, the prognostic significance of mutated PTEN exons has not ever been described.

Sixty-seven endometrial carcinomas were analyzed for PTEN mutations using single-strand conformation polymorphism analysis and DNA sequencing. First, survival rates were compared according to PTEN status and mutated PTEN exons. Subsequently, univariate and multivariate analyses of various favorable prognostic factors for survival were conducted. The associations between PTEN mutation and clinicopathological features were also statistically evaluated.

PTEN mutations were detected in 37 of 67 (55%) specimens. Among 47 mutations, frameshifts (57%) and mutations in exon 8 (38%) were most frequent. In univariate analysis, a factor of PTEN mutation only outside exons 5–7 was associated with significantly better survival (P = 0.02), although mutation in any exon of PTEN was not (P = 0.33). Subsequent multivariate analysis revealed that factors of mutation only outside exons 5–7 of PTEN, stage I/II, and G₁ were significant and independent prognostic indicators for favorable 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 features.

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.

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