UTERI OF WOMEN WITH ENDOMETRIAL CARCINOMA CONTAIN A HISTOPATHOLOGICALSPECTRUM OF MONOCLONAL PUTATIVE PRECANCERS, SOME WITH MICROSATELLITE INSTABILITY

We have tested the hypothesis that endometrial precancers persist in u teri of patients with endometrial carcinoma and are monoclonal, Twenty -two hysterectomies with both well-differentiated endometrial adenocar cinoma and adjacent (normal or abnormal) noncancerous endometrium unde rwent successful clonal analysis using a PCR assay for nonrandom X chr omosome inactivation, Monoclonal lesions included endometrial carcinom a, endometrial polyps, and atypical endometrial hyperplasias, whereas normal and anovulatory endometrium were polyclonal, Comparison of the specific X chromosome copy preferentially inactivated by the matched m onoclonal cancers and associated monoclonal lesions allowed us to excl ude polyps, but not endometrial hyperplasias, as potential precancers, The repetitive genetic marker (HUMARA) for X inactivation was altered in some cancers, permitting identification of microsatellite instabil ity (RER+), Two patients with RER+ cancers also had adjacent RER+ hype rplasias. The seven monoclonal and two RER+ hyperplasias had focal or diffuse cytological atypia, a feature previously associated with risk for endometrial cancer, We conclude that: (a) putative endometrial pre cancers and cancers share a monoclonal growth pattern; (b) cancers wit h microsatellite instability may acquire this feature as precancers; a nd (c) monoclonal endometrial precancers have the morphology of hyperp lasias, which vary in the extent of cytological atypia and degree of a rchitectural complexity.