Geographic distribution of co-dominant DNA stemlines in breast carcinoma.

Abstract

Breast carcinomas often contain multiple DNA stemlines in flow cytometric DNA histograms. However, due to mixing during tissue disaggregation the microanatomical relationship between the cells which comprise distinct stemlines is unclear. We performed image cytophotometric DNA analysis (IA) on two separate areas of intact tissue sections of 19 breast carcinomas which were selected on the basis of flow cytometric (FCM) DNA content heterogeneity (i.e., multiple stemlines). For comparison, similar analyses were performed on seven tumors with unimodal FCM DNA histograms. Six of the 7 tumors (86%) with unimodal FCM histograms were also unimodal in both IA DNA histograms. Among tumors with heterogeneous FCM DNA histograms, the presence of multiple stemlines was confirmed in IA DNA histograms in 16/19. In nine of these 16 cases, multiple DNA stemlines having similar DNA indices were present in both areas of neoplasm examined with IA. The remaining seven cases displayed unimodal IA histograms in both areas, however DNA indices differed between the two histograms. These findings imply that cell populations corresponding to flow cytometrically detected DNA stemlines are often intimately admixed, even within geographically separated portions of breast tumors. This pattern suggests that productive interactions between genetically distinct tumor populations may lead to stable co-dominance of ancestral clones during progression of some breast carcinomas.