Ploidy Level and Tumor Progression in Prostatic Carcinoma

Abstract

Methods developed for cytophotometric analysis of archival tumor specimens used in retrospective studies were evaluated quantitatively. Up to 20-year-old May-Grünwald-Giemsa stained cytological slides could be Feulgen stained with excellent results. By expressing DNA data from the tumor cells as relative values (c-values) related to the internal staining control (mean value 2c) detailed ploidy level determinations could be made as accurately from measurements of old, destained slides as from measurements of cells from fresh tumor material, which were directly Feulgen-stained. Ploidy level determinations of prostatic carcinoma in 213 patients selected on the basis of survival time were analyzed. By studying the tumors in two extreme groups (extreme group I: 131 patients who died from prostatic cancer within 3 years of diagnosis, and extreme group II: 82 patients who survived more than 15 years after diagnosis) it was possible to evaluate in detail the optimal limits for defining the diploid 2c-region and tetraploid 4c-region. Using these limits to determine the percentage of aberrant tumor cells, i.e. non 2c and non 4c, and combining this with the modal value (in c units) of the tumor cell population the tumors could unambigously be divided into near-diploid-D-, near-tetraploid-T, T- and highly aneuploid A-types. The prognostic significance of ploidy level was studied in prostatic carcinoma in a non-selected group of patients subjected to endocrine therapy and long-term clinical follow-up (up to 23 years). This patient group consisted of all of the patients who were diagnosed as having prostatic carcinoma by means of fine-needle aspiration biopsy at the Karolinska Hospital during 1966. The A-type tumors progressed rapidly and killed 96% of the patients within 5 years (and all patients within 7 years). D- and T-type tumors progressed much more slowly. None of the patients with these tumors died from the tumor disease within the first 5 years after diagnosis, and 12% of the patients (crude survival) were still alive 15 years after diagnosis. Ploidy level was superior to morphological grade and clinical stage (tumor size) as a prognostic indicator.