Ploidy disturbances as an early indicator of intrinsic malignancy in endometrial carcinoma

The need for a postoperative treatment of patients with highly aggressive endometrial cancer necessitates more specific and accurate prognostic indicators.

In a prospective study, 88 samples from 72 endometrial tumors were subjected to microfluorometric single-cell DNA analysis to assess the DNA content of the main stemline and the ploidy distribution histogram. The histologic grade of differentiation, architecture, and mitotic index (MI) also were evaluated as biologic characteristics of neoplastic cells.

The main stemline was peridiploid in 44 of 72 cases, peritetraploid in 4 of 72, and aneuploid in 24 of 72. High ploidy levels (> 3 c) were associated strictly with papillary and solid architecture, high MI, and undifferentiated grade. Multiple analyses of different sites showed stable ploidy values in 11 of 13 cases; 2 solid tumors changed from showing peridiploidy to peritetraploidy in one of the three sites examined. The number of S-phase and greater than G2 cells (heteroploid index) was compared with MI and showed six tumors with histogram irregularities probably resulting from intratumor genetic instability. Survival information was available for 65 patients with a mean observation period of 50 months. A single parameter, high ploidy level (> 3 c), was the most important determinant of survival at all stages; its prognostic value was fundamental in patients with Stage I disease, in whom DNA content showed higher independent significance (P < 0.001) than the other histologic and clinical factors considered.

These studies suggest that DNA content is a biologic characteristic firmly associated with tumor aggressiveness; DNA analysis could offer early and objective evidence of an intrinsic highly malignant phenotype.