Loss of heterozygosity in fibrocystic change of the breast - Genetic relationship between benign proliferative lesions and associated carcinomas

Loss of heterozygosity (LOH), a genetic change frequently detected In cance r, can also occur in benign epithelial foci in the breast. To characterize LOH in benign breast tissue, 32 cases containing the various components of fibrocystic change in the absence of malignancy were studied. Microdissecte d foci of ductal hyperplasia, apocrine metaplasia, sclerosing adenosis, and morphologically normal terminal duct lobular units (TDLUs) were analyzed f or LOH at 14 polymorphic loci representing seven chromosomal arms. LOH was detected in 22% of normal TDLUs (6/27), 17% of adenosis (4/23), 19% of hype rplasia (4/21), and 53% of apocrine metaplasia (10/19) specimens. Because o f the high percentage of LOH in apocrine metaplasia In nonneoplastic specim ens, the genetic relationship between apocrine metaplasia and cancer was st udied in a panel of breast cancer cases. Of 14 examples of apocrine metapla sia adjacent to a carcinoma, seven were found to have LOH with at least one marker, in all seven cases, the tumor and apocrine metaplasia shared LOH a t one or more markers. The results demonstrate that LOH occurs frequently i n the components of fibrocystic change as well, as in normal TDLUs and sugg est that foci of apocrine metaplasia can share a genetically altered precur sor cell with an associated carcinoma.