Microglandular adenosis or microglandular adenoma? A molecular genetic analysis of a case associated with atypia and invasive carcinoma Felipe C Geyer, Yael B Kushner, 1 Maryou B Lambros, Rachael Natrajan, Alan Mackay, Narinder Tamber, Kerry Fenwick, Dave Purnell, 2 Alan Ashworth, Rosemary A Walker 3 & Jorge S Reis-Filho The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK, 1 Department of Pathology, McGill University Health Center, McGill University, Montreal, QC, Canada, 2 Department of Histopathology, University Hospitals of Leicester NHS Trust and 3 Department of Cancer Studies and Molecular Medicine, University of Leicester School of Medicine, Leicester, UK Date of submission 12 Feburary 2009 Accepted for publication 11 May 2009 Geyer F C, Kushner Y B, Lambros M B, Natrajan R, Mackay A, Tamber N, Fenwick K, Purnell D, Ashworth A, Walker R A & Reis-Filho J S (2009) Histopathology 55, 732–743 Microglandular adenosis or microglandular adenoma? A molecular genetic analysis of a case associated with atypia and invasive carcinoma Aims: Microglandular adenosis (MGA) is a rare breast lesion, which has long been considered to be hyper- plastic. However, atypical forms of MGA (AMGA) and invasive carcinomas arising in the background of MGA are recorded. Recent studies have suggested that MGA may be a non-obligate precursor of invasive carcinomas that are negative for hormone receptors and lack HER-2 overexpression (triple- negative phenotype). The aim of this study was to determine whether MGA is clonal and whether it harbours chromosomal aberrations similar to those found in matched invasive ductal carcinoma of no special type (IDC-NST). Methods and results: We report on a case comprising MGA, AMGA and a high-grade IDC-NST. The three components were separately microdissected and sub- jected to genetic analysis with high-resolution micro- array comparative genomic hybridisation. Identical genetic changes were detected in all components with subsequent acquisition of additional genetic aberra- tions in the invasive component, suggesting that MGA was the substrate for the development of the invasive carcinoma. Immunohistochemistry revealed concor- dant profiles across all components, characterized by triple-negative phenotype and variable positivity for basal markers. Conclusions: Similar to adenomas, MGA is, at least in some cases, a clonal lesion and may be a non-obligate precursor of a subgroup of high-grade triple-negative and basal-like breast carcinomas. Keywords: basal-like, breast cancer, comparative genomic hybridization, microglandular adenosis, triple-negative Abbreviations: aCGH, microarray comparative genomic hybridization; AMGA, atypical microglandular adenosis; BAC, bacterial artificial chromosome; CAV, caveolin; cCGH, chromosomal comparative genomic hybridization; CISH, chromogenic in situ hybridization; CK, cytokeratin; EGFR, epidermal growth factor receptor; ER, oestrogen receptor; FISH, fluorescence in situ hybridization; IDC-NST, invasive ductal carcinoma of no special type; MGA, microglandular adenosis; PR, progesterone receptor Address for correspondence: J S. Reis-Filho, MD, PhD, FRCPath, The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK. e-mail: jorge.reis-filho@icr.ac.uk and R Walker, FRCPath, Department of Cancer Studies and Molecular Medicine, University of Leicester, RKCSB, Leicester Royal Infirmary, Leicester LE2 7LX, UK. e-mail: raw14@le.ac.uk Ó 2009 The Authors. Journal compilation Ó 2009 Blackwell Publishing Limited. Histopathology 2009, 55, 732–743. DOI: 10.1111/j.1365-2559.2009.03432.x