Rare in Other Common Gynecological Malignancies Are Frequent in Endometrial Carcinoma

Loss of heterozygosity of chromosome lOq has been reported in ap proximately 40% of endometrial carcinomas. PTEN, a candidate tumor suppressor gene located at chromosome 10q23.3, was recently identified and found to be homozygously deleted or mutated In several different types of human tumors. To determine If PTEN is a target of lOq loss of heterozygosity in carcinomas of the endometrium, we examined 32 pri mary endometrial carcinomas for mutations in PTEN. The tumors in cluded the two major histopathological types of endometrial carcinoma: endometrioid (n 26; 14 microsatellite instability (MI)-positive and 12 MI-negative) and serous (a = 6). Overall, mutations were detected in 50% of theendometrialcarcinomasweanalyzed.Mutationswerepresentin 12 of 14 (86%) MI-positiveand 4 of 12 (33%) MI-negativeendometnoid tumors. Furthermore, mutations were found in all three histological grades of MI-positive endometriold carcinoma. All six serous endometrial carcinomas lacked detectable mutations. To evaluate the role of PTEN in other common malignancies of the female genital tract, 12 serous ovarian carcinomas and 10 squamous cervical carcinomas were analyzed and were negative for mutations. Our results support PTEN as a tumor suppressor gene and suggest that mutations In PTEN play a significant role in the pathogenesis of the endometrioid type of endometrial carcinoma.