Intratumoral heterogeneity of DNA indexes in transitional cell bladder cancer: relation to tumor histology.

DNA flow cytometry (FCM) was performed from multiple samples in 60 transitional cell bladder carcinomas (TCC) to detect intratumoral heterogeneity of DNA index (DI). The samples for analysis were selected randomly and they were paraffin-embedded peroperative biopsy specimens from the primary TCCs. Intratumoral heterogeneity of DI was found in 12 of 60 (20%) samples. All WHO grade I tumors were diploid whereas 12 of 41 (29%) WHO grade II-III tumors showed a heterogeneous DI. DI heterogeneity was related to WHO grade (p = 0.004), mitotic frequency (p = 0.002), inflammatory cell infiltration (ICI; p = 0.003) and nonpapillar growth pattern (p = 0.06). In multivariate analysis, the WHO grade (p = 0.027) and the degree of ICI (p = 0.041) were independently related to heterogeneous DI. The results show that (a) many of the WHO grade II-III TCCs are composed of diploid and aneuploid cell populations; (b) the presence of dense ICI and TCCs may lead to false diploid DI. Consequently, the analysis of multiple samples is recommended in WHO grade II-III tumors to detect aneuploidy particularly when dense ICIs are present.