Image cytophotometric DNA histogram heterogeneity in adenocarcinoma of the breast

In 36 breast carcinomas, DNA histograms derived from the edge of an invasive primary tumor were compared with those of a second area in the invasive tumor (n = 10) or of corresponding in situ (n = 22) and/or (nodal) metastatic (n = 6) components using image cytophotometry on formalin-fixed, paraffin-embedded sections. DNA aneuploidy (defined by comparison with diploid host stroma cells) was identified in the invasive areas of 26/36 (72%), the noninvasive foci of 16/22 (73%) and the metastases of 5/6 (83%). Ploidy status of different areas of invasive tumor were concordant in all (10/10) cases; however, the in situ and invasive areas exhibited different DNA content determinations in 5/22 (23%), and metastases differed from the primary neoplasm in 3/6 (50%). Moreover, clonal DNA content heterogeneity, defined as the presence of more than one discrete G0/G1 population, was observed in 20/36 (56%) tumors examined. Clonal heterogeneity was generally manifest as bimodal DNA histograms in one (n = 11) or both (n = 4) components of a tumor. Also, most DNA histogram heterogeneity was due to the presence of diploid range (n = 11) or near-tetraploid (n = 6) neoplastic populations accompanying DNA aneuploid clones. The remaining heterogeneous cases were unimodal in both components analyzed but exhibited aneuploid stemlines with different DNA indices (n = 2) or a diploid range population in one histogram and an aneuploid population in the other (n = 3). We conclude that DNA content heterogeneity is frequent in breast carcinoma and, in large part, may be accounted for by near-diploid or near-tetraploid stemlines, which are difficult to resolve from benign host elements in flow cytometric histograms.