Flow-cytometric analysis of nuclear DNA content in endometrial adenocarcinoma. Atypical mitoses are associated with DNA aneuploidy.

Abstract

Flow-cytometric studies have demonstrated that DNA aneuploidy and proliferative activity are independent prognostic factors in endometrial carcinoma. The authors performed flow-cytometric analysis of the nuclear DNA content of 46 fresh endometrial adenocarcinomas to investigate tumor DNA ploidy and cell-cycle kinetics in relation to histologic features with known prognostic significance, mitotic activity (assessed quantitatively), and clinical features suggestive of hyperestrogenism. Thirty-five tumors (76%) were DNA-diploid, and 11 (24%) were DNA-aneuploid. DNA aneuploidy correlated significantly with two histologic features: high cytologic grade (P < .027) and five or more atypical mitoses per 50 high-power fields (P < .001). The presence of one or more atypical mitosis per 50 high-power fields, evaluated independent of DNA ploidy, was associated with stage III or IV tumors (P < .015). A low proliferative index correlated with tumors with grade 1 architecture (P < .006) and grade 1 or 2 cytology (P < .017); a high proliferative index correlated with vascular invasion by tumor (P < .027). DNA ploidy and proliferative activity did not correlate with any feature indicative of estrogenic status including age, parity, menopausal status, obesity, hypertension, diabetes, exogenous estrogen use, or endometrial hyperplasia. Therefore, in endometrial adenocarcinoma, estrogenic status does not correlate with DNA ploidy or proliferative activity; proliferative activity correlates with tumor grade; and atypical mitoses appear to be highly associated with both DNA aneuploidy and advanced tumor stage, and as such, may identify tumors with a poor prognosis.