The MYC oncogene in breast cancer progression: from benign epithelium to invasive carcinoma

One hypothesis for breast cancer development suggests that breast carcinogenesis involves a progression of events leading from benign epithelium to hyperplasia (with or without atypia) to carcinoma in situ and then invasive carcinoma. The MYC gene (alias c-Myc) is a transcriptional regulator whose expression is strongly associated with cell proliferation and cell differentiation. The present study is a descriptive analysis of MYC status throughout the hypothesized stages of invasive ductal carcinoma progression. A tissue microarray (TMA) was constructed including representative selected areas (normal cells, hyperplasia, in situ carcinoma, and invasive carcinoma) from each of 15 patients. Fluorescence in situ hybridization (FISH) with the LSI c-MYC/CEN8/IgH probe was performed. Two cases displayed MYC amplification (13%), showing this amplification only in the invasive carcinoma zones selected. Five cases displayed polysomy of chromosome 8 (33%), detected only in ductal in situ and invasive zones selected. Benign lesions and normal adjacent cells were classified as normal. None of the hyperplasia specimens and normal specimens analyzed showed any alterations in MYC status or any aneusomies of chromosome 8. The presence of MYC amplification only in invasive cells suggests that the finding of MYC amplification could reflect an advanced tumor progression.