IMAGE CYTOPHOTOMETRIC DNA HISTOGRAM HETEROGENEITY IN ADENOCARCINOMA OF THE BREAST

In 36 breast carcinomas, DNA histograms derived from the edge of an in vasive 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 (n odal) metastatic (n = 6) components using image cytophotometry on form alin-fixed, paraffin-embedded sections. DNA aneuploidy (defined by com parison with diploid host stroma cells) was identified in the invasive areas of 26136 (72%), the noninvasive foci of 16122 (73%) and the met astases of 516 (83%). Ploidy status of different areas of invasive tum or were concordant in all (10/10) cases; however, the in situ and inva sive areas exhibited different DNA content determinations in 5122 (23% ), and metastases differed from the primary neoplasm in 316 (50%). Mor eover, clonal DNA content heterogeneity, defined as the presence of mo re than one discrete G0/G1 population, was observed in 20/36 (56%) tum ors examined. Clonal heterogeneity was generally manifest as bimodal D NA histograms in one (n = 11) or both (n = 4) components of a tumor. A lso, most DNA histogram heterogeneity was due to the presence of diplo id range (n = 11) or near-tetraploid (n = 6) neoplastic populations ac companying DNA aneuploid clones. The remaining heterogeneous cases wer e unimodal in both components analyzed but exhibited aneuploid stemlin es with different DNA indices (n = 2) or a diploid range population in one histogram and an aneuploid population in the other (n = 3). We co nclude that DNA content heterogeneity is frequent in breast carcinoma and, in large part, may be accounted for by near-diploid or near-tetra ploid stemlines, which are difficult to resolve from benign host eleme nts in flow cytometric histograms.