DNA-PLOIDY AND PROLIFERATION HETEROGENEITY IN HUMAN PROSTATE CANCERS

DNA ploidy determinations have been shown to have clinical application in predicting disease progression, survival, or response to anti-andr ogen therapies in prostate carcinomas, Since intra-tumor heterogeneity may have a profound effect on DNA measurements, we determined the fre quency of DNA ploidy and proliferation (here S-phase fraction) heterog eneity in early prostatic carcinomas, and estimated the potential impa ct of heterogeneity on predicting disease course, survival, or respons e to therapy. Using image and flow cytometric analysis of archival, pa raffin-embedded prostate tumors, we measured DNA ploidy in individual foci of prostatic carcinoma in stage T1a, T1b and T1c disease, Image a nalysis studies included the use of Feulgen stained tissue sections, a nd a comparison of these results with flow cytometric DNA ploidy deter minations on nuclei isolated from the same tumor foci, Flow cytometry was also used to measure DNA index and tumor S-phase fraction, in some cases using multiparameter analysis of isolated nuclei to determine D NA content and the level of the proliferation-associated antigen, p105 . Our results indicate that DNA aneuploid foci of prostate carcinoma a re infrequently seen in stage T1a disease (13% of the individuals stud ied), and that the presence of both DNA diploid and aneuploid foci in the same sample is seen in less than 10% of these individuals, Stage T 1b and T1c tumors containing only DNA diploid nuclei are seen, though these are likely most common in low volume, low Gleason grade tumors, By using now cytometry to compare these results with those using image analysis of the same tumor foci, we demonstrated that the majority (> 75%) of these aneuploid tumors are DNA tetraploid, Our data on prostat e tumor S-phase fractions indicate that DNA diploid tumors generally h ave a lower S-phase than DNA aneupoloid foci (including comparisons of DNA diploid and aneuploid foci in the same prostate tumor), These res ults support the model that early prostate tumors are DNA diploid and have a low S-phase, and that these tumors likely evolve to DNA tetrapl oid tumors with a similar low S-phase fraction. (C) 1995 Wiley-Liss, I nc.