MUTATIONS IN PTEN ARE FREQUENT IN ENDOMETRIAL CARCINOMA BUT RARE IN OTHER COMMON GYNECOLOGICAL MALIGNANCIES

Loss of heterozygosity of chromosome 10q has been reported in approxim ately 40% of endometrial carcinomas, PTEN, a candidate tumor suppresso r gene located at chromosome 10q23.3, was recently identified and foun d to be homozygously deleted or mutated in several different types of human tumors, To determine if PTEN is a target of 10q loss of heterozy gosity in carcinomas of the endometrium, we examined 32 primary endome trial carcinomas for mutations in PTEN, The tumors included the two ma jor histopathological types of endometrial carcinoma: endometrioid (n = 26; 14 microsatellite instability (MI)-positive and 12 MI-negative) and serous (n = 6), Overall, mutations were detected in 50% of the end ometrial carcinomas we analyzed, Mutations were present in 12 of 14 (8 6%) MI-positive and 4 of 12 (33%) MI-negative endometrioid tumors, Fur thermore, mutations were found in all three histological grades of MI- positive endometrioid carcinoma, All six serous endometrial carcinomas lacked detectable mutations, To evaluate the role of PTEN in other co mmon malignancies of the female genital tract, 12 serous ovarian carci nomas and 10 squamous cervical carcinomas were analyzed and were negat ive for mutations, Our results support PTEN as a tumor suppressor gene and suggest that mutations in PTEN play a significant role in the pat hogenesis of the endometrioid type of endometrial carcinoma.