PTEN mutations in endometrial carcinomas: A molecular and clinicopathologic analysis of 38 cases

PTEN mutations have been reported to be frequent in endometrioid carcinomas of the endometrium (EEC). Some correlation has been found between PTEN mut ations and the presence of microsatellite instability (MI) in EEC, but no c onvincing cause-effect relationship for such association has been offered. DNA of 38 patients with endometrial carcinoma (EC) was extracted from blood and from fresh-frozen and paraffin-embedded tumor tissue. PTEN mutations w ere detected by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. Results were correlated with MI status and clinicopatholog ic data. PTEN mutations were detected in 17 tumors (44.7%), and they were m ore frequent in endometrioid (EEC) (17 of 33, 51.5%) than in nonendometrioi d carcinomas (NEEC) (0 of 5, 0%). PTEN mutational spectrum differed between MI+ and MI-tumors. PTEN mutations were detected in 9 of 15 MI+ tumors (60% ), but in only 8 of 23 MI- neoplasms (34.8%). In EC with MI, PTEN mutations were detected in short coding mononucleotide repeats (A)5 and (A)(6) in 4 of 9 carcinomas (44.4%). These results confirm that PTEN is an important ta rget gene in endometrial carcinogenesis. The occurrence of PTEN mutations i n short coding mononucleotide repeats in MI-positive tumors suggests that t hese mutations may be secondary to deficiencies in mismatch repair and give s some explanation for the frequent presence of PTEN mutations in these tum ors. Copyright (C) 2000 by W.B. Saunders Company.