High cell kinetics is associated with amplification of the int‐2, bcl‐1, myc and erbB‐2 proto‐oncogenes and loss of heterozygosity at the DF3 locus in primary breast cancers

Abstract

Cell kinetics is a predictive parameter of breast‐cancer aggressiveness, and mutations occurring in mammary tumorigenesis may favor uncontrolled cell proliferation. In this study, cell kinetics, clinico‐pathological characteristics and genetic alterations at the int‐2, bcl‐1, c‐myc, c‐erbB‐2, and DF3 loci were analyzed and correlated in 54 primary breast carcinomas. The occurrence of mutations at more than one locus was also studied. Tumor‐proliferative activity was evaluated by determination 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 the 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. Alone, allele loss at the DF‐3 locus was not significantly associated with 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. Multiple mutations were found only in less differentiated tumors, which included the 2 cases from the youngest patients of the series. © 1995 Wiley‐Liss, Inc.