Intratumoral variations in DNA ploidy and s‐phase fraction in human breast cancer

Article type: Research Article

Authors: Arnerlöv, Conny^; | Emdin, Stefan O. | Cajander, Stefan | Bengtsson, Nils‐Olof | Tavelin, Björn | Roos, Göran

Affiliations: Department of General Surgery, Umeå University Hospital, S‐901 85 Umeå, Sweden | Department of Pathology, Umeå University Hospital, S‐901 85 Umeå, Sweden | Department of Oncology, Umeå University Hospital, S‐901 85 Umeå, Sweden

Note: [] Corresponding author. Tel.: +46 90 785 0000; Fax: +46 90 7851 156; E‐mail: [email protected].

Abstract: To study intratumoral DNA ploidy heterogeneity and S‐phase fraction (SPF) variability, we prospectively collected five different samples from 48 breast carcinomas and each sample was analysed separately by flow cytometry. Aneuploidy rate was 89.6% after analysis of four or five samples. DNA ploidy heterogeneity, i.e., different samples classified as either DNA euploid or DNA aneuploid in the same tumor was seen in 17%, and DNA index heterogeneity, i.e., tumor populations with different DNA indices (DIs) seen in different samples was 44%. A statistical model defining SPF heterogeneity is proposed. SPF heterogeneity as defined by us was 71%, and as expected the SPF heterogeneity rate increased significantly with increasing number of analysed samples. Four or more samples are needed to detect the most deviant (highest) SPF values. An unrecognized intratumor heterogeneity of DNA ploidy and SPF may partly explain the conflicting results reported in the literature on the above prognostic indicators.

Keywords: Breast cancer, DNA ploidy, heterogeneity, s‐phase fraction, SPF

Journal: Analytical Cellular Pathology, vol. 23, no. 1, pp. 21-28, 2001