Molecular Evidence in Support of the Neoplastic and Precursor Nature of Microglandular Adenosis
Felipe C Geyer, Magali Lacroix-Triki, Pierre-Emmanuel Colombo, Neill Patani, Arnaud Gauthier, Rachael Natrajan, Maryou B Lambros, Ibrahim Khalifeh, Constance Albarracin, Sandra Orru, Caterina Marchio, Anna Sapino, Alan Mackay, Britta Weigelt, Fernando C Schmitt, Jelle Wesseling, Nour Sneige, Jorge S Reis-Filho. Hospital Israelita Albert Einstein, Sao Paulo, Brazil; Institut Claudius Regaud, Toulouse, France; CRLC Val d'Aurelle, Montpellier, France; The Institute of Cancer Research, London, United Kingdom; Institut Curie, Paris, France; The American University of Beirut Medical Center, Beirut, Lebanon; The University of Texas MD Anderson Cancer Centre, Houston; Ospedale A. Businco, Cagliari, Italy; University of Turin, Turin, Italy; Cancer Research UK London Research Institute, London, United Kingdom; Institute of Molecular Pathology and Immunology (IPATIMUP), Oporto, Portugal; Netherlands Cancer Institute, Amsterdam, Netherlands
Background: Microglandular adenosis (MGA) is a proliferative breast lesion associated with hormone receptor- and human epidermal growth factor receptor 2- (HER2) negative (i.e. triple-negative phenotype) invasive carcinomas. Previous studies have demonstrated that MGA may be a clonal proliferation and precursor of triple-negative breast cancers. The aim of this study was to determine whether MGAs harbour genetic alterations similar to those found in matched invasive carcinomas.
Design: A series of 12 cases composed of MGA and/ or atypical MGA (AMGA), ten associated with invasive carcinoma, was retrieved. Expression of oestrogen (ER) and progesterone (PR) receptors, HER2, S100, cytokeratin (CK) 8/18, high molecular weight CKs and EGFR was investigated using immunohistochemistry. The morphologically distinct components of each case (MGA, AMGA and/ or invasive carcinoma) were microdissected and subjected to high-resolution microarray-based comparative genomic hybridisation.
Results: Immunohistochemical profiling revealed that all invasive carcinomas were of triple-negative phenotype and expressed S100, cytokeratins 8/18 and 'basal' markers. Apart from three typical MGAs, including one not associated with breast cancer, all samples analysed were found to harbour gene copy number aberrations, demonstrating the clonal nature of the majority of MGAs. Copy number changes were detected on average in 20.3% (median 15.0%, range 0.5-61.9%) of the genome, indicating varying levels of genetic instability. In three cases, MGA/AMGA displayed copy number aberrations similar to those found in matched invasive components (Pearson r≥0.67, p<0.05).
Conclusions: Our results provide circumstantial evidence that MGA was the substrate for invasive carcinoma development and support the contention that MGA can be a clonal lesion and a non-obligate precursor of triple-negative breast cancer.
Monday, March 19, 2012 1:00 PM
Poster Session II # 78, Monday Afternoon