Different proliferative patterns characterize different preinvasive breastlesions

The study of cell-cycle associated proteins Ki-67/MIB-1, bcl-2 and p53 coul d clarify some features regarding the early phases of neoplastic progressio n in the breast. An extensive immunohistochemical study was carried out of the expression of these markers in all kinds of preinvasive breast lesions and their collateral normal parenchyma, a type of analysis not previously r eported. The specimens were 35 florid ductal hyperplasias (FDHs), 8 atypica l ductal hyperplasias (ADHs), 12 well-differentiated intraductal carcinomas (WDICs), 20 intermediately differentiated intraductal carcinomas (IDICs), 14 poorly differentiated intraductal carcinomas (PDICs), 12 atypical lobula r hyperplasias (ALHs), 12 type-A lobular carcinomas in situ (LCIS), 150 nor mal small-size ducts and 365 lobules. All FDHs, ADHs, WDICs, and lobular le sions showed low proliferation (Ki-67/MIB-1), bcl-2 positivity, and p53 neg ativity; all PDICs expressed high proliferation, while 85 per cent and 7 pe r cent were p53 and bcl-2 positive respectively; IDICs showed high prolifer ation (50 per cent), bcl-2 expression (70 per cent), and p53 positivity (30 per cent), but no correlation between the expression of these markers was observed. Independent of the type of collateral lesion and age of the patie nt, 90 per cent and 10 per cent of small ducts/lobules showed low and high proliferation and diffuse and low bcl-2 expression respectively; no p53 pos itivity was observed. The modulation of cell proliferation and apoptosis co ntrol in ductal lesions could be the expression of a progression from hyper plasia/WDIC to PDIC, in which IDICs represent the link, owing to their immu noprofile. An alternative purely speculative hypothesis is that the differe nt immunoprofile of the preinvasive lesions reflects their different origin in normal breast parenchyma. Low proliferative or bcl-2 positive lobules c ould be the site of origin of the lesions maintaining this phenotype, namel y FDHs, ADHs, WDICs and lobular lesions, while highly proliferative or bcl- 2 negative lobules could be the site in which PDICs develop. Consequently, preinvasive breast lesions could express a different regulation of apoptosi s control and proliferative activity from the very beginning, rather than a modulation during neoplastic progression. Copyright (C) 1999 John Whey & S ons, Ltd.