Heterogeneous versus homogeneous genetic nature of multiple foci of in situ carcinoma of the breast.

The vast majority of in situ breast cancers represent focal lesions all derived from a single clone and requiring local treatment alone. We focused our attention on rare cases of multicentric in situ carcinomas affecting different quadrants, which required mastectomy. Defining the origin from single- or multiple-cell clones of separate independent neoplastic foci in the breast may be of pathogenetic interest and of importance in deciding the type of therapy to be administered. We employed a molecular assay based on loss of heterozygosity (LOH) and human androgen receptor assay (HUMARA) analysis of microdissected samples from 19 mastectomies. Two or more tissue samples were obtained from 7 patients with multicentric lobular in situ carcinoma (LCIS), either classical or large-cell variety; and 12 patients with multicentric ductal in situ carcinomas (DCIS), either low-grade (7 cases) or high-grade (5 cases) variety. Separate foci of high-grade (comedonic) DCIS were found to be monoclonal in nature. On the contrary, definite evidence favoring the origin from different cell clones of separate carcinomatous foci within the same breast was obtained in 2 cases of low-grade DCIS and in 6 cases of LCIS. A genetic imbalance might be the factor favoring the development of multifocal heterogeneous foci of in situ breast cancer. Such a small subgroup of in situ cancers affecting diffusely the entire breast and originating from independent foci presents both clinical and pathogenetic interest.