Ductal epithelial proliferations of the breast: a biological continuum? Comparative genomic hybridization and high-molecular-weight cytokeratin expression patterns

According to current concepts, benign proliferative breast disease (BPBD) i s a direct precursor of breast cancer, in a spectrum ranging: from ductal h yperplasia to overtly invasive carcinoma. In this study, comparative genomi c, hybridization (CGH) was used to screen ductal hyperplasia and other BPBD lesions and ductal carcinoma in situ (DCIS) for common genomic abnormaliti es, to test the relationship between these hyperplastic and neoplastic lesi ons. Immunohistochemistry for cytokeratin 5/6 was used as a diagnostic adju nct to distinguish ductal hyperplasia from DCIS. A total of 42 cases of BPB D comprising ductal hyperplasia of the usual type (n = 14), papilloma (n = 22), tubular adenoma (it = 3), and adenosis (n = 3), as well as 52 cases of DCIS, were studied. All cases of BPBD consistently displayed the presence of a subpopulation: of cytokeratin 5/6-expressing basal-type cells within t he proliferative lesion, whereas all of the non-high-grade and most of the high-grade DCIS lesions lacked cytokeratin 5/6-positive cells. Whereas gros s genomic alterations, as determined by CGH, were undetectable in BPBD, dis tinct genetic changes characterized all cases of DCIS, with one exception. These results confirm the usefulness of cytokeratin 5/6 immunohistology in the diagnosis of BPBD and neoplastic breast lesions and support the view th at BPBD and DCIS are not closely related entities and that BPBD is not an o bligate direct precursor of DCIS. Copyright (C) 2001 John Wiley & Sons, Ltd .