DCC GENETIC ALTERATIONS AND EXPRESSION IN ENDOMETRIAL CARCINOMA

DCC (Deleted in Colorectal Carcinoma) is a candidate tumor suppressor gene located on the long arm of chromosome 18, DCC was initially ident ified and cloned during a search for the target gene located in a regi on of 18q that demonstrated loss of heterozygosity (LOH) in 70 to 80% of colorectal cancers, More recently, the region of 18q harboring the DCC gene has been shown to undergo LOH in approximately 14 to 30% of e ndometrial carcinomas, These findings suggest that DCC may be a target of LOH in at least some endometrial carcinomas and, therefore, may ha ve a role in the pathogenesis of this common malignancy of the female genital tract To address this possibility, we analyzed 26 cases of end ometrioid endometrial carcinoma for DCC LOH and alterations in an AT m icrosatellite repeat located in an intron of the DCC gene. LOH was det ected in one case (4%). Allelic shifts at the DCC AT repeat were detec ted in five (19%) additional cases, We also evaluated DCC protein expr ession by immunohistochemical analysis in normal, hyperplastic, and ne oplastic endometrial tissues. Three proliferative and five secretory e ndometria and one simple endometrial hyperplasia demonstrated staining for DCC, Four of the 26 endometrioid endometrial carcinomas for which frozen tissue was available, including at least one from each histolo gic grade, and a case of endometrioid carcinoma confined to the endome trium completely lacked detectable staining for DCC. Although DCC LOH was infrequent in endometrial carcinomas, alterations of the gene (LOH or AT repeat alterations) were not uncommon (23% of our cases), In ad dition, DCC was expressed in normal endometrial tissue, whereas expres sion was lost in all of the five endometrial carcinomas, The combinati on of the genetic alterations and loss of DCC protein expression sugge sts that inactivation of the DCC gene may play a role in the pathogene sis of endometrial carcinoma.