Evaluation of tumor heterogeneity of prostate carcinoma by flow- and imageDNA cytometry and histopathological grading

Background. Heterogeneity of prostate carcinoma is one of the reasons for p retreatment underestimation of tumor aggressiveness. We studied tumor heter ogeneity and the probability of finding the highest tumor grade and DNA ane uploidy with relation to the number of biopsies. Material and methods. Specimens simulating core biopsies from five randomly selected tumor areas from each of 16 Bocking's grade II and 23 grade III p rostate carcinomas were analyzed for tumor grade and DNA ploidy by flow- an d fluorescence image cytometry (FCM, FICM). Cell cycle composition was meas ured by FCM. Results. By determination of ploidy and cell cycle composition, morphologic ally defined tumors can further be subdivided. Heterogeneity of tumor grade and DNA ploidy (FCM) was 54% and 50%. Coexistence of diploid tumor cells i n aneuploid specimens represents another form of tumor heterogeneity. The p roportion of diploid tumor cells decreased significantly with tumor grade a nd with increase in the fraction of proliferating cell of the aneuploid tum or part. The probability of estimating the highest tumor grade or aneuploid y increased from 40% for one biopsy to 95% for 5 biopsies studied. By combi ning the tumor grade with DNA ploidy, the probability of detecting a highly aggressive tumor increased from 40% to 70% and 90% for one and two biopsie s, respectively. Conclusion. Specimens of the size of core biopsies can be used for evaluati on of DNA ploidy and cell cycle composition. Underestimation of aggressiven ess of prostate carcinoma due to tumor heterogeneity is minimized by simult aneous study of the tumor grade and DNA ploidy more than by increasing the number of biopsies. The biological significance of coexistent diploid tumor cell in aneuploid lesions remains to be evaluated.