Heterogeneity index score (HIS). New computerized method for classification of human bladder carcinomas using flow cytometry.

The rationale for studying nuclear DNA may be its direct relationship to the aggressiveness of cancer. Recent flow cytometric studies (FCM) of cancer cells show the limitation of the current methods for the accurate determination of the degree of aneuploidy or proliferative characteristics of a tumor cell. Here we report a new methodology for a computerized determination which is well correlated with relative mean DNA content in cell populations analyzed by FCM (heterogeneity index, HI). A total of seventy-six tissue samples were examined. Twenty-two specimens were benign tissue while fifty-four were histologically malignant bladder tumors. Forty tumors were grade (G)I-II, ten G-III, and four carcinoma in situ. The samples were mechanically minced into a single cell suspension and stained with propidium iodide. An Ortho system 50-H multiparameter flow cytometer equipped with an Ortho 2150 computer was used to determine DNA content and cell number. HI was calculated using the following formulas: (formula; see text) The mean HIS of twenty-two normal and benign tissues was 9.805 +/- 5.6. The forty G-II tumors had a mean HIS of 23.576 +/- 26.519. Statistical differences were observed between benign tissue and G-I-II tumors (P = 0.0196). G-III tumors had a marked increase in HIS of 160.965 +/- 63.404. The limited study of four carcinoma in situ tumors showed a mean HIS of 45.4 +/- 9.5. Our computer extrapolation of flow cytometric DNA analysis quantifies an objective description of FCM characteristics and histochemical index which may distinguish the degree of tumor malignancy.