Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN benign endometrial cyst of the ovary: Possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary

Loss of heterozygosity (LOH) at locus 10q23.3 and mutation of the PTEN tumo r suppressor gene occur frequently in both endometrial carcinoma and ovaria n endometrioid carcinoma, To investigate the potential role of the PTEN gen e in the carcinogenesis of ovarian endometrioid carcinoma and its related s ubtype, clear cell carcinoma, we examined 20 ovarian endometrioid carcinoma s, 24 clear cell carcinomas, and 34 solitary endometrial cysts of the ovary for LOH at 10q23.3 and point mutations within the entire coding region of the PTEN gene. LOH was found in 8 of 19 ovarian endometrioid carcinomas (42 .1%), 6 of 22 clear cell carcinomas (27.3%), and 13 of 23 solitary endometr ial cysts (56.5%). In 5 endometrioid carcinomas synchronous with endometrio sis, 3 cases displayed LOH events common to both the carcinoma and the endo metriosis, 1 displayed an LOH event in only the carcinoma, and 1 displayed no LOH events in either lesion. In 7 clear cell carcinomas synchronous with endometriosis, 3 displayed LOH events common to both the carcinoma and the endometriosis, 1 displayed an LOH event in only the carcinoma, and 3 displ ayed no LOH events in either lesion. In no cases were there LOH events in t he endometriosis only. Somatic mutations in the PTEN gene were identified i n 4 of 20 ovarian endometrioid carcinomas (20.0%), 2 of 24 clear cell carci nomas (8.3%), and 7 of 34 solitary endometrial cysts (20.6%). These results indicate that inactivation of the PTEN tumor Suppressor gene is an early e vent in the development of ovarian endometrioid carcinoma and clear cell ca rcinoma of the ovary.