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

• Published in: Human pathology 2000-03, Vol.31 (3), p.312-317
• Main Authors: Bussaglia, Elena, del Rio, Elisabeth, Matias-Guiu, Xavier, Prat, Jaime
• Format: Article
• Language: English
• Subjects: Adenocarcinoma, Clear Cell - genetics; Adenocarcinoma, Clear Cell - pathology; Biological and medical sciences; carcinogenesis; Carcinoma, Endometrioid - genetics; Carcinoma, Endometrioid - pathology; coding mononucleotide repeats; Cystadenocarcinoma, Papillary - genetics; Cystadenocarcinoma, Papillary - pathology; DNA Mutational Analysis; DNA, Neoplasm - analysis; endometrial carcinoma; Endometrial Neoplasms - genetics; Endometrial Neoplasms - pathology; endometrioid carcinoma; Female; Female genital diseases; Germ-Line Mutation - genetics; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; microsatellite instability; Microsatellite Repeats; molecular pathology; mutations; Phosphoric Monoester Hydrolases - genetics; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; PTEN; PTEN Phosphohydrolase; Tumor Suppressor Proteins; Tumors
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/S0046-8177(00)80244-0

PTEN mutations have been reported to be frequent in endometrioid carcinomas of the endometrium (EEC). Some correlation has been found between PTEN mutations and the presence of microsatellite instability (MI) in EEC, but no convincing 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 were detected by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. Results were correlated with MI status and clinicopathologic data. PTEN mutations were detected in 17 tumors (44.7%), and they were more frequent in endometrioid (EEC) (17 of 33, 51.5%) than in nonendometrioid 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 target gene in endometrial carcinogenesis. The occurrence of PTEN mutations in short coding mononucleotide repeats in MI-positive tumors suggests that these mutations may be secondary to deficiencies in mismatch repair and gives some explanation for the frequent presence of PTEN mutations in these tumors.