Gene amplifications detected by fluorescence in situ hybridization in pureintraductal breast carcinomas: Relation to morphology, cell proliferation and expression of breast cancer-related genes

Investigation of early breast carcinogenesis is limited by the difficulty i n obtaining cell cultures or adequate fresh frozen material and by the fact that available data from in situ techniques are interpreted in terms of va rious classification systems. Our studies in a series of pure ductal carcin omas in situ (DCIS) were conducted in accordance with the recommendations o f the international Consensus Conference (Hum. Pathol., 28, 122-125, 1997) relative to processing, determination of lesion extent, and histological st ratification primarily on nuclear grade (NC), A multifactorial study perfor med in 15 low- and 16 high-NC DCIS (68% detested by mammography) included t he following: (1) morphological analysis of NC, necrosis, and architectural pattern; (2) detection of numerical genomic abnormalities at ERBB2, MYC, C CND1, Xq1.2 and 20q13 loci by fluorescence in situ hybridization on interph ase nuclei; and (3) immunohistochemical determination of cell proliferation , p53 accumulation, hormonal receptors and bcl-2 expression on serial secti ons of formalin-fixed, paraffin-embedded specimens, High NC, comedo/solid p attern and necrosis were significantly associated with amplification at one or more loci, the number of amplified loci, amplification at the ERBB2 loc us, absence of bcl-2 and hormonal receptor expression and high cell prolife ration (p < 0.05). High NC and comedo/solid pattern were significantly asso ciated with MYC amplification and p53 accumulation, and necrosis with CCND1 amplification (the only gene amplification detected in low NC DCIS), These data provide additional information on the early steps of breast carcinoge nesis, in accordance with currently recognized criteria of histological cla ssification. (C) 2000 Wiley-Liss, Inc.