Biopathological significance of single cell DNA aneuploidy measured by static cytometry in breast cancer

DNA ploidy image analysis in breast carcinomas has occasionally revealed cases with a diploid DNA content but with a single hypertetraploid element, the so-called single cell aneuploidy (SCA). To identify the biologic significance of this little known phenomenon, we selected 40 cases with SCA from a series of 599 consecutive operable breast carcinomas. The clinical, pathological and biological characteristics of SCA cases were compared with those of a control group of 40 pure diploid breast carcinomas. Hormonal receptor status, proliferative indexes (Ki-67) and p53 overexpression were determined immunohistochemically and quantitatively evaluated by image analysis. The overexpression of c-erbB-2 was determined semiquantitatively. SCA was observed in 6.6% of cases (40 of 599) and in 17% of otherwise diploid cases (40 of 236). Breast cancers with SCA occur in younger women (mean age 54.75 y vs 61.12 y, P<0.05), are smaller (mean diameter 20.00 vs 21.62 mm), less differentiated (percentage of G3 cases 13.2 vs 2.9), more frequently hormone independent (ER positivity 70.0 vs 77.5%; PgR positivity 57.5 vs 77.5%) and have a greater cell proliferative activity (mean S-phase: 4.6 vs 2.8, P<0.05), (percentage of Ki-67 immunostaining: 24.1 vs 19.7%). There is also more overexpression of c-erbB-2 and P53, particularly in pT1 cases in which the percentage of c-erbB-2 positive cells is 54 vs 32 (P value is not significant) and the percentage of p53 is 29 vs 4 (P<0.05). According to these results SCA may be a reliable marker of genetic instability and of greater biologic aggressiveness. Image cytometry of DNA content may be a cost effective means of identifying breast cancer patients with an increased risk of tumour recurrences despite otherwise favourable prognostic parameters.