Incidence of chromosomes 1 and 17 aneusomy in breast cancer and adjacent tissue: An interphase cytogenetic study

Background: Characterization of the biopathologic events underlying the ear ly steps of breast carcinogenesis may have a dramatic impact on reducing br east cancer mortality. Genes involved in breast tumorigenesis are localized on chromosomes 1 and 17, and numeric aberrations of these chromosomes have been correlated with breast cancer tumorigenesis and progression. Accordin g to the field cancerization hypothesis, specific chromosome aberrations ma y be present in breast cancer and in normal-appearing adjacent tissue. The latter changes reflect the genomic damage that follows longterm carcinogeni c exposure and precede the morphologically detectable neoplastic transforma tion. We hypothesize that detection of these aberrations in benign breast e pithelium may provide a tool for molecular risk assessment. Study Design: Using fluorescence in situ hybridization with centromere-spec ific probes, we determined the status of chromosomes 1 and 17 in fresh impr ints of 28 samples of primary tumors and 54 samples of their surrounding un involved parenchyma taken from patients undergoing operations for breast ca rcinoma. Ten contralateral breast biopsy specimens collected from patients with previous breast carcinoma were also evaluated as a surrogate of a high -risk group to rule out the hypothesis that chromosomal aneusomy in tumor-a djacent tissue could be related to a paracrine effect of the primary tumor Ten samples of benign breast tissue taken from patients at low risk were us ed as controls to define tolerance limits for aneusomy definition. Results: Using threshold values of 40% of signal loss and 13% of signal gai n to define chromosome aneusomy tie, mean + 3 SDs of the control group sign als), we found the following: 1) almost all primary breast tumors were aneu somic for chromosomes 1 and 17; 2) primary breast tumor and adjacent uninvo lved parenchyma shared the same pattern of chromosomes 1 and 17 aneusomy in 66.7% of patients; and 3) chromosomes 1 and 17 aneusomies in contralateral benign breast samples from high-risk patients were not different from thos e in primary breast tumor or adjacent tissue samples. Conclusions: These results suggest that chromosomes 1 and 17 aneusomy may r epresent an intermediate biomarker of breast tumorigenesis potentially usef ul to detect patients at high risk of breast carcinoma who may benefit from preventive interventions. (J Am Cell Surg 2000;130:530-539. (C) 2000 by th e American College of Surgeons).