Flow Cytometric Determination of DNA Content in Renal Cell Carcinoma with Special Reference to Tumor Heterogeneity

Abstract

The DNA (deoxyribonucleic acid) content in 111 samples from 14 renal cell carcinomas (8 samples per one tumor specimen) was analyzed by flow cytometry to investigate DNA heterogeneity in renal cell carcinomas and DNA ploidy patterns were also compared with histologic grade and tumor stage. Of the 50 grade I and 22 grade II tumor samples, 46 (92%) and 14 (64%) were diploid respectively, but only 5 (13%) of 39 grade III & IV samples were diploid. This was statistically significant (p=O.OI). Of the 9 pT2NoNo tumors, diploid were 4 (44%) and of 5 pT3NanyMo tumors (4 T3aNoMo, 1 T3bN1Mo), diploid was 1 (20%). No statistical correlation was made between tumor stage and ploidy status, because of the small number of specimens. Tumor heterogeneity was noted in 8 of 14 tumors (57%). Of the 6 homogeneous tumors, five were diploid and one was aneuploid. Of the 9 aneuploid tumors (64%), only one (7%) was homogeneously aneuploid and 8 (57%) were heterogeneously aneuploid. The probability of having an aneuploid sample by taking at random 1, 2, 3, 4 samples from a tumor specimen was 65%, 88%, 94% and 97%, respectively. In conclusion, renal cell carcinoma is heterogenous in terms of DNA ploidy. For flow cytometric evaluation at least 4 samples need to be analyzed to minimize the sampling error and obtain aneuploidy with 95% confidence in one tumor specimen.