CLONAL HETEROGENEITY IN BREAST-CANCER - KARYOTYPIC COMPARISONS OF MULTIPLE INTRA-TUMOROUS AND EXTRA-TUMOROUS SAMPLES FROM 3 PATIENTS

Intratumor phenotypic heterogeneity is one of the characteristics of b reast carcinomas, and genetic mechanisms are likely to contribute to i t. We have studied breast cancer clonal heterogeneity by cytogenetic a nalysis of multiple tumor samples (one from each tumor quadrant) as we ll as samples of macroscopically normal surrounding breast tissue from 3 patients with this disease. Clonal chromosome aberrations were foun d in all 8 successfully analyzed samples from the carcinomas. Two to 6 cytogenetically unrelated clones were detected in each case, unevenly distributed among the tumor quadrants. Karyotypic abnormalities were also found in 4 out of 9 macroscopically tumor-free samples from the s urrounding tissue; in 2 of these samples, a ductal carcinoma in situ w as detected histologically, and the cytogenetic evidence suggests that the remaining 2 samples also contained neoplastic cells. Quantitative analysis of the findings revealed a statistically significant higher frequency of karyotypically abnormal cells in samples with a histologi c diagnosis of carcinoma vs. samples without any detected malignancy. That cells bearing cytogenetic evidence that they belong to the tumor parenchyma are left behind during breast-conserving surgery for carcin oma of the breast may account for the relatively high long-term local relapse rates seen in this disease. (C) 1995 Wiley-Liss, Inc.