KARYOTYPIC COMPARISONS OF MULTIPLE TUMOROUS AND MACROSCOPICALLY NORMAL SURROUNDING TISSUE SAMPLES FROM PATIENTS WITH BREAST-CANCER

Many tumor tissues are made up of genetically different cell populatio ns, and the study of the causes and consequences of this heterogeneity must play a central role in cancer research. We have studied breast c ancer clonal heterogeneity by cytogenetic analysis of 4123 cells from 52 successfully short-term-cultured tumorous, metastatic, and macrosco pically normal breast tissue samples from 6 women with this disease. A ll 7 carcinomas (one woman had bilateral disease) contained 1 to 9 kar yotypically related as well as unrelated clones, unevenly distributed among the tumor quadrants. Two clonal chromosome abnormalities were re current: interstitial 3p deletions were found in 5 carcinomas, whereas del(1)(q42) was detected in another 2 tumors. Both successfully analy zed metastatic lesions (one axillary lymph node and one metastasis in the subcutis) contained only one of several clones present in the prim ary tumor, thus exemplifying a reduction in overall karyotypic complex ity during carcinoma spreading. In the case with the cytogenetically a bnormal lymph node, another karyotypically unrelated clone was found t o invade locally in the surrounding breast; also, histological evidenc e of carcinoma infiltration was seen in these tissue samples. In none of the other cases were clonal karyotypic changes found in macroscopic ally normal, extratumorous breast tissue. We conclude that a large pro portion of breast carcinomas are polyclonal with cytogenetically disti nct cell subpopulations expanding within separate domains of the growi ng tumor. Karyotypically disparate neoplastic cells may have different capacities to display malignancy-specific features (e.g., to grow inv asively and set up distant metastases). It is presumed that their syne rgetic action is required for the full-blown carcinoma phenotype.