HIGH CELL-KINETICS IS ASSOCIATED WITH AMPLIFICATION OF THE INT-2, BCL-1, MYC AND ERBB-2 PROTOONCOGENES AND LOSS OF HETEROZYGOSITY AT THE DF3 LOCUS IN PRIMARY BREAST CANCERS

Cell kinetics is a predictive parameter of breast-cancer aggressivenes s, and mutations occurring in mammary tumorigenesis may favor uncontro lled cell proliferation. In this study, cell kinetics, clinico-patholo gical characteristics and genetic alterations at the int-2, bcl-1, c-m yc, c-erbB-2, and DF3 loci were analyzed and correlated in 54 primary breast carcinomas. The occurrence of mutations at move than one locus was also studied. Tumor-proliferative activity was evaluated by determ ination of the thymidine labeling index (TLI). Amplification (AMP) of int-2 was observed in 11.2%, of bcl-1 in 9.4%, of c-myc in 5.7% and of c-erbB-2 in 8.6% of the carcinomas. Loss of heterozygosity (LOH) at t he DF3 locus was detected in 13.9% of the tumors. Genetic alterations demonstrated a significant association with patient's age and high TLI values. AMP and LOH + AMP did not appear to be statistically related to histotype, histological grade, tumor size or lymph-node status. Alo ne, allele loss at the DF-3 locus was not significantly associated wit h any of the clinico-pathological characteristics studied. Alterations at more than one locus, including int-2/bcl-1, int-2/c-myc, int-2/bcl -1/c-erbB-2, and c-myc/DF3, were detected in 11.1% of the tumors. Mult iple mutations were found only in less differentiated tumors, which in cluded the 2 cases from the youngest patients of the series. (C) 1995 Wiley-Liss, Inc.