Cancer biology for individualized therapy: correlation of growth fraction index in native-state histoculture with tumor grade and stage.

There is a need for individualization of all aspects of cancer therapy. Because of significant heterogeneity within a tumor class, there is a need to develop an in vitro test to accurately gauge tumor aggressiveness. Such a measurement would greatly aid treatment decision making. Current methodologies such as flow cytometry, which lacks unambiguous interpretation of cell-proliferative data, and determination of the thymidine-labeling index, which measures nucleotide uptake in a nonphysiological state, have not reproducibly attained this goal. We have developed an in vitro native-state three-dimensional gel-supported histoculture system that allows the growth of all human solid tumor types for relatively long time periods. The native-state system was used to identify the percent of cells capable of incorporating [3H]thymidine over a 4-day period, which we term the growth fraction index (GFI). We have compared the ability of cancer tissue to proliferate in native-state culture to the stage and histological grade of four major types of human carcinomas: breast, ovarian, colon, and lung. Eighty percent of tumor explants could be evaluated, even when sent from across the country. We have determined that the GFI correlates with tumor stage and grade for breast and ovarian carcinoma. In colon carcinoma, there is a trend toward higher GFIs in tumors of more advanced stage and grade. In non-small cell lung carcinomas, GFI, stage, and grade do not correlate. These results suggest the applicability of gel-supported three-dimensional native-state histoculture for prognostic purposes in patients with breast and ovarian cancers and demonstrate the clinical relevance of the native-state histoculture system.