Microglandular adenosis or microglandular adenoma? A molecular genetic analysis of a case associated with atypia and invasive carcinoma

Authors


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

Abstract

Aims:  Microglandular adenosis (MGA) is a rare breast lesion, which has long been considered to be hyperplastic. 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 subjected to genetic analysis with high-resolution microarray comparative genomic hybridisation. Identical genetic changes were detected in all components with subsequent acquisition of additional genetic aberrations in the invasive component, suggesting that MGA was the substrate for the development of the invasive carcinoma. Immunohistochemistry revealed concordant 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.

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