Clonal profiling of mixed lobular and ductal carcinoma revealed by multiplex ligation‐dependent probe amplification and fluorescence in situ hybridization

A needle biopsy of a mass in the right breast of a 36‐year‐old woman revealed invasive ductal carcinoma ( IDC ), and approximately 20% of cancer cells showed unequivocal membranous staining with the H ercep T est. After systemic therapy with trastuzumab and paclitaxel followed by FEC (fluorouracil + epirubicin + cyclophosphamide), a right mastectomy was performed. By histological and immunohistochemical examinations, the resected tumor consisted mainly of E ‐cadherin‐negative invasive lobular carcinoma ( ILC ), and the rest was ERBB 2‐positive IDC ; thus, the diagnosis was mixed ductal and lobular carcinoma. Multiplex ligation‐dependent probe amplification and fluorescence in situ hybridization ( FISH ) analyses revealed that ILC and IDC shared high‐level amplification of CCND 1 in homogeneously staining regions ( HSR ) and that IDC had an additional HSR ‐type amplicon of ERBB 2 . These findings strongly indicate that IDC and ILC had a common precursor cell with CCND 1 amplification. Review of the biopsy specimen with FISH showed IDC with gene amplifications of CCND 1 and ERBB 2 as a minor component, IDC without amplification of CCND 1 or ERBB 2 as a major component, and a minute portion of ILC with CCND 1 amplification. We speculate that chemotherapy and trastuzumab caused a marked reduction in IDC ; however, ILC with CCND 1 amplification was resistant to chemotherapy and grew.