Ovarian carcinoma heterogeneity as demonstrated by DNA ploidy

In ovarian carcinoma, DNA ploidy measured by flow cytometric (FCM) analysis is an independent prognostic factor. However, limited sampling may underestimate the extent of ploidy variation (i.e., heterogeneity). Uncovering these hidden populations may explain poor outcomes in patients with ostensibly favorable ploidy patterns. The authors examined ploidy in a mean of 6.4 tumor samples per patient to better assess the occurrence of heterogeneity.

FCM analysis was performed on multiple samples from 19 cases of advanced, serous ovarian carcinoma. Tumors were considered as heterogeneous by two definitions: (1) the presence of more than one ploidy pattern (e.g., diploidy and tetraploidy); and (2) the existence of DNA indices of sufficient variation so as to characterize two distinct populations of neoplastic cells.

With the first definition, 47% (9 of 19) of the tumors were heterogeneous, 37% (7 of 19) homogeneous-aneuploid, and 16% (3 of 19) homogeneous-diploid. These three groups showed no significant differences in histologic type, grade, patient age, stage, or survival. With the second definition, 27% (4 of 15) of the non-diploid cases were heterogeneous and 73% (11 of 15) were homogeneous. When these two groups were compared as to type, grade, patient age, and stage, no significant differences were demonstrated. However, the median survival of the patients with heterogeneous tumors was significantly longer (P < 0.05) than the survival of patients with homogeneous tumors.

Ovarian carcinoma heterogeneity is high when multiple sites are assayed. This suggests conservative interpretation of ploidy when only a single sample is analyzed and examination of multiple samples when practicable.