title: Clonal profiling of mixed lobular and ductal carcinoma revealed by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.
abstract: 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 HercepTest. 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 ERBB2-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 CCND1 in homogeneously staining regions (HSR) and that IDC had an additional HSR-type amplicon of ERBB2. These findings strongly indicate that IDC and ILC had a common precursor cell with CCND1 amplification. Review of the biopsy specimen with FISH showed IDC with gene amplifications of CCND1 and ERBB2 as a minor component, IDC without amplification of CCND1 or ERBB2 as a major component, and a minute portion of ILC with CCND1 amplification. We speculate that chemotherapy and trastuzumab caused a marked reduction in IDC; however, ILC with CCND1 amplification was resistant to chemotherapy and grew.
authors.affiliation: Department of Molecular and Cellular Pathology, Kanazawa University, Ishikawa.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tajiri
authors.forename: Masafumi
authors.initials: M
authors.lastname: Inokuchi
authors.forename: Seiko
authors.initials: S
authors.lastname: Sawada-Kitamura
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kawashima
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Nakamura
authors.forename: Takeru
authors.initials: T
authors.lastname: Oyama
authors.forename: Yoh
authors.initials: Y
authors.lastname: Dobashi
authors.forename: Akishi
authors.initials: A
authors.lastname: Ooi
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001707:Biopsy, Needle; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D016172:DNA Fingerprinting / Q000379:methods*; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008408:Mastectomy; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019938:Cyclin D1; D004273:DNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; C530104:CCND1 protein, human; C508053:ERBB2 protein, human
keywords: FISH; MLPA; breast cancer; ductal carcinoma; lobular carcinoma