Microsatellite instability in endometrial carcinomas: frequent replication errors in tumors of early onset and/or of...

Endometrial and ovarian carcinomas are common among women belonging to hereditary nonpolyposis colorectal carcinoma (HNPCC) families; tumors developing in them are characterized by genetic instability due to an inherited dysfunction of the DNA-mismatch-repair system. To clarify the role of similar genetic factors in sporadic forms of gynecological tumors, we examined 77 endometrial and 68 ovarian carcinomas for replication error (RER) at five microsatellite loci. RER-positive phenotypes at two or more microsatellite loci were observed in 18 of the endometrial carcinomas, but in only two of the ovarian carcinomas. Among the patients with endometrial carcinomas, the frequency of RER tended to be higher in those under age 50 than in those over age 60. Furthermore, RER was significantly more frequent in poorly differentiated than in well-differentiated tumors (P = 0.008, Fisher's exact test). These data suggest that genetic factors characterized by RER are likely to play an important role in some endometrial carcinomas, particularly those of early onset and/or of the poorly differentiated type.