Different proliferative patterns characterize different preinvasive breast lesions.

The study of cell-cycle associated proteins Ki-67/MIB-1, bcl-2 and p53 could clarify some features regarding the early phases of neoplastic progression 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 reported. The specimens were 35 florid ductal hyperplasias (FDHs), 8 atypical ductal hyperplasias (ADHs), 12 well-differentiated intraductal carcinomas (WDICs), 20 intermediately differentiated intraductal carcinomas (IDICs), 14 poorly differentiated intraductal carcinomas (PDICs), 12 atypical lobular hyperplasias (ALHs), 12 type-A lobular carcinomas in situ (LCIS), 150 normal small-size ducts and 365 lobules. All FDHs, ADHs, WDICs, and lobular lesions showed low proliferation (Ki-67/MIB-1), bcl-2 positivity, and p53 negativity; all PDICs expressed high proliferation, while 85 per cent and 7 per cent were p53 and bcl-2 positive respectively; IDICs showed high proliferation (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 patient, 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 positivity was observed. The modulation of cell proliferation and apoptosis control in ductal lesions could be the expression of a progression from hyperplasia/WDIC to PDIC, in which IDICs represent the link, owing to their immunoprofile. An alternative purely speculative hypothesis is that the different immunoprofile of the preinvasive lesions reflects their different origin in normal breast parenchyma. Low proliferative or bcl-2 positive lobules could be the site of origin of the lesions maintaining this phenotype, namely 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 apoptosis control and proliferative activity from the very beginning, rather than a modulation during neoplastic progression.