BENIGN BREAST DISEASE - ABSENCE OF GENETIC ALTERATIONS AT SEVERAL LOCI IMPLICATED IN BREAST-CANCER MALIGNANCY

Benign breast disease (BED) is a heterogeneous group of benign breast problems that has been associated with breast cancer risk by several i nvestigators, Genetic alterations have been described in breast carcin omas under the headings of loss of heterozygosity (1p, 3p, 70, 11p, 17 p, 17 and 18q), mutations (p53, c-H-ras-1), and/or gene amplifications (c-myc, int-2/FGF3, and c-erbB-2/neu). In an attempt to determine whe ther these genetic alterations might also be involved in the developme nt of BED, we have analyzed such alterations in 50 BED lesions. The hi stological types of samples studied were: 37 fibroadenomas; 8 benign p hyllode tumors; and 5 fibrocytic diseases. Cellular DNA was extracted from tissues and from corresponding blood leukocytes according to stan dard techniques, digested with appropriate restriction endonucleases, and analyzed by Southern blot. The following are informative cases fou nd in a total number of patients analyzed for each locus: 13 of 26 for L-myc (1p); 9 of 23 for THRB (3p); 11 of 29 for met (7q); 27 of 50 fo r c-a-ras-l (11p); 3 of 13 for TP53 (17p); 14 of 50 for D17S30 (17p); 20 of 33 for D17S4 (17q); and 13 of 33 for D18S5 (18q). No loss of het erozygosity was detected at any of the examined loci. Alternatively, n one of the 50 BED cases displayed an amplification of the three genes tested (c-myc, int-2/FGF3, and c-erbB-2/neu). Our results show that mo lecular alterations, which are more frequently involved in malignant b reast carcinomas, do not occur in BED lesions, These results indicate that these molecular alterations could constitute late events in the p athogenesis of breast carcinomas.