DETECTION OF ALLELIC IMBALANCE INDICATES THAT A PROPORTION OF MAMMARYHYPERPLASIA OF USUAL TYPE ARE CLONAL, NEOPLASTIC PROLIFERATIONS

Previously, we developed methodology for studying allelic imbalance (A l) in preinvasive breast disease and showed that Al identified at vari ous chromosomal loci in invasive carcinoma is already present in in si tu carcinoma and atypical hyperplasia. We now extend this work by look ing for Al in hyperplasia of usual type (HUT), apocrine cysts (AC), an d papilloma (Pap) of the breast. HUT, AC, and Pap were identified in f ormalin-fixed, paraffin-embedded sections of benign breast biopsies an d isolated using a microdissection technique. Al was investigated usin g polymorphic microsatellite markers and PCR. Al was identified in 3/2 3 (13%) informative cases of HUT at 17q (D17S250), 2/43 (4.7%) at 17p (D17S796), 1/22 (4.5%) at 16q (D16S413), and 0/18 (0%) at 13q (D13S267 ). No particular histologic feature of HUT predicted the presence of A l. No examples of AC or Pap exhibited Al at any of the markers studied . Al previously identified at various chromosomal loci in invasive car cinoma, in situ carcinoma, and atypical hyperplasia is present at low frequency in HUT in benign breast biopsies but not in AC or Pap. The p ossibility that Al in the latter could be masked by contamination from stromal and myoepithelial cells cannot, however, be excluded at this stage. At least a proportion of HUT thus appear to be clonal (neoplast ic) rather than hyperplastic proliferations as their name suggests. Th e significance of Al in the pathogenesis of HUT or its subsequent prog ression to carcinoma is not yet clear and requires further investigati on.