Genomic Profiling of Mitochondria-Rich Breast Cancer
JS Reis-Filho, D de Biase, MBK Lambros, FC Geyer, M Ragazzi, R Natrajan, A Mackay, N Tamber, K Fenwick, A Ashworth, G Tallini, V Eusebi. ICR, London, United Kingdom; University of Bologna, Bologna, Italy
Background: Breast carcinomas entirely composed of cells with abundant eosinophilic cytoplasm fall into four main groups: apocrine, neuroendocrine, acinic and oncocytic carcinomas. Oncocytic carcinomas are composed of mitochondria-rich cells (mitochondria-rich breast cancer: mt-rich BC) and their status as a discrete pathological entity remains a matter of contention. Our aim was to define the molecular genetic features of mt-rich BCs using high-resolution microarray-based comparative genomic hybridisation (aCGH) and to compare these profiles with those of a series of grade and oestrogen receptor (ER) status-matched invasive ductal carcinomas of no special type (IDC-NST).
Design: Eighteen mt-rich BCs were retrieved from the files of the Department of Pathology at Bellaria Hospital, University of Bologna. Cases were graded according to Elston & Ellis and ER was assessed using the Ventana system. Eighteen mt-rich BCs and a series of 36 grade and ER matched IDC-NSTs were microdissected and subjected to aCGH using a 32K tiling path bacterial artificial chromosome array platform. aCGH results were subjected to unsupervised hierarchical clustering analysis. Profiles were compared using a previously validated multi-Fisher's exact test with p values adjusted for multiple comparison by the false discovery rate.
Results: Unsupervised analysis demonstrated that mt-rich BC preferentially formed a distinct cluster. Multi-Fisher's exact test revealed that mt-rich BC significantly differed from IDC-NSTs at the genomic level. Gains on chromosomes 3q29, 5q35.2, 6p21.31, 7q22.1, 8p11.1, 9q34.11, 11q13.1-q13.2, 12q13.13, 16p13.3, 17q21.2, 19q13.12-19q13.2 and 20q11.21, and losses on 2p11.2, 3p12.2, 4p15.32, 5q21.3, 6p22.1, 7q31.31-q31.32, 10q23.1, 11p14.1, 12q24.11, 14q13.3-q21.1, 15q15.1-q15.3, 18q21.32, 21q21.3 and Xq13.1 were more prevalent in mt-rich BC. High-level gains/amplifications of chromosome 5q23.2, 6q24.2, 7q34, 8q23.1-q23.2, 9q34.3 and 17q25.3 were significantly associated with mt-rich BC.
Conclusions: Our study provides the first high-resolution molecular genetic analysis of mt-rich BCs, which revealed that these tumours are heterogeneous at the genetic level. Mt-rich BCs have distinct histological features and molecular genetic profiles supporting the contention that they may constitute a distinct pathological entity.
Monday, March 9, 2009 1:00 PM
Poster Session II # 39, Monday Afternoon