Nuclear DNA analysis: DNA heterogeneity in the monitoring of patients with locally advanced prostatic carcinoma.

Abstract

Single-cell DNA cytophotometry was employed to analyze the tumors of 271 patients with locally advanced prostatic carcinoma as to DNA ploidy and heterogeneity and the distribution of the phases of the cell cycle before and during therapy, with the intention of establishing prognostic factors apart from those already known (stage, grade). Follow-up periods ranged from 1 to 9 years. 198 (73%) of the 271 patients had carcinoma stage T3 N0 M0, and 73 (27%) of them had carcinoma stage T3/T4 N+M1. The tumors were evaluated cytologically to establish the grades of malignancy. 11.8% were grade I carcinoma, 64.3% were grade II and 23.9% were grade III carcinoma. Single-cell DNA cytophotometry demonstrated aneuploidy rates of up to 73% and diploidy rates of up to 23.8% for the higher grades of malignancy, whereas the diploidy rate established for grade I carcinoma was 71% and the respective aneuploidy rate was 15.2%. These differences are significant (p < 0.001). There was a significant correlation between the results of DNA cytophotometry and the clinical course of the disease. Patients with diploid tumor cell nuclei developed no metastases and no local tumor progression during the follow-up period of 9 years, whereas patients with aneuploid tumor cell nuclei showed metastases and local tumor progression within 8-22 months, despite changes in therapy. These patients died of carcinoma after an average 18 months following primary diagnosis.