The S-phase fraction of the aneuploid cell subpopulation is the biologically relevant one in aneuploid breast cancers

Abstract

Background. In the case of DNA-aneuploid tumors there are no clear guidelines as to which S-phase fraction is the more relevant one: that corresponding to either the diploid or the aneuploid population, or rather an average of both.

Materials and methods. We studied 280 breast cancer specimens from previously untreated patients. Histologically, 231 were ductal infiltrating carcinomas, 30 lobular infiltrating carcinomas and 19 corresponded to other, less frequent varieties. Postsurgically, 164 cases (58.6%) were classified as T1, 87 (31.1%) as T2 and 7 as T3. The remaining 22 cases were multifocal, diffuse tumors. Flow cytometry was performed on fresh tumor tissue, and immunohistochemistry for hormone receptors, Ki67, c-erb-B2 and p53 on paraffin-embedded material.

Results. In diploid tumors, a high S-phase (above the 75th percentile) correlated significantly with Ki67 expression ≥20% (p<0.0001). In aneuploid tumors, however, this was only the case for the aneuploid fraction of tumor cells (p<0.0001). A high S-phase of diploid tumors correlated directly and significantly with a high histologic grade (p=0.04), a high nuclear grade (p=0.01), tumor size (p=0.0008), and inversely with estrogen (p<0.0001) and progesterone (p<0.0001) receptor expression. In aneuploid tumors, the aneuploid tumor fraction showed a direct and significant correlation with a high histologic grade (p=0.005), a high nuclear grade (p=0.001), mutant p53 expression (p=0.0009), and inversely with estrogen (p<0.0001) and progesterone (p=0.0001) receptor expression. A high S-phase of the diploid cell fraction of aneuploid tumors, on the other hand, just showed an inverse correlation with high nuclear grade of the tumors (p=0.02), and none whatsoever with all other tested parameters.