Showing papers by "George L. Mutter published in 1996"

Allelotype Mapping of Unstable Microsatellites Establishes Direct Lineage Continuity between Endometrial Precancers and Cancer

Abstract: Progressive microsatellite changes in replication error positive (RER+) endometrium were used to reconstruct evolutionary stages of nonfamilial adenocarcinoma. RER+ putative endometrial precancers (atypical endometrial hyperplasias) progress to RER+ carcinomas, which retain some of the altered microsatellites acquired in earlier precursor stages. The RER+ phenotype may provide a specific marker for early-stage endometrial neoplasms that cannot be resolved by routine histopathology and may be a useful tool to stratify stages in the evolution of RER+ tumors.

Uteri of Women with Endometrial Carcinoma Contain a Histopathological Spectrum of Monoclonal Putative Precancers, Some with Microsatellite Instability

Abstract: We have tested the hypothesis that endometrial precancers persist in uteri of patients with endometrial carcinoma and are monoclonal. Twenty-two hysterectomies with both well-differentiated endometrial adenocarcinoma and adjacent (normal or abnormal) noncancerous endometrium underwent successful clonal analysis using a PCR assay for nonrandom X chromosome inactivation. Monoclonal lesions included endometrial carcinoma, 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 monoclonal cancers and associated monoclonal lesions allowed us to exclude 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 instability (RER+). Two patients with RER+ cancers also had adjacent RER+ hyperplasias. 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 precancers and cancers share a monoclonal growth pattern; (b) cancers with microsatellite instability may acquire this feature as precancers; and (c) monoclonal endometrial precancers have the morphology of hyperplasias, which vary in the extent of cytological atypia and degree of architectural complexity.

Clonal Analysis of Sacrococcygeal “Teratomas”

Abstract: Congenital masses of the sacrococcygeal region commonly contain multiple tissues and have variously been subclassified as neoplasms or congenital hamartomas based on clinicopathological and embryological observations. We have used a polymerase chain reaction-based assay for nonrandom X chromosome inactivation to infer the clonality of three congenital sacrococcygeal tumors previously diagnosed as teratomas. One solid immature teratoma was monoclonal, and a predominantly cystic histologically mature mass was polyclonal. A third immature teratoma was noninformative because of baseline asymmetry of polyclonal tissue X inactivation. We confirm that immature teratomas at this site appear to be monoclonal neoplasms and suggest that at least some histologically mature “teratomas” are more appropriately classified as hamartomas.