Genetic changes in paired atypical and usual ductal hyperplasia of the breast by comparative genomic hybridization

Purpose: Breast cancer is thought to develop from noninvasive precursor les ions, although the earliest steps of neoplastic transformation are still un defined. Usual ductal hyperplasia (UDH) is considered to represent a benign proliferation of ductal epithelial cells, whereas atypical ductal hyperpla sia (ADH) may represent the first clonal neoplastic expansion of these cell s. The aim of this study was to examine genetic alterations in UDH and ADH and to determine the relationship between these lesions in the same breast biopsy. Experimental Design: Comparative genomic hybridization analysis was used to define copy number alterations in DNA extracted from archival sections of 18 patients. Nine patients showed ADH with adjacent UDH, and nine showed pu re UDH. None showed evidence of invasive cancer or ductal carcinoma in situ . Results: Five of the nine ADH lesions showed chromosome copy number alterat ions. 16q loss (five cases) and 17p loss (two cases) were the most frequent changes. The associated UDH lesions in these five patients also showed cop y number alterations, always a subset of the changes present in the paired ADH. In one other patient, the UDH showed eight chromosomal alterations, wh ereas the paired ADH showed no changes. Only one of nine cases with pure UD H showed comparative genomic hybridization abnormalities. Conclusions: These data support the likelihood that UDH is a precursor of A DH, at least in some cases representing neoplastic growth. The frequencies of 16q and 17p losses suggest that alterations of candidate genes located i n these chromosomal regions may play a role early in breast carcinogenesis.