Molecular Characterisation of Mucinous Carcinomas of the Breast – A Genomic Profiling Analysis
M Lacroix-Triki, P Saurez, MB Lambros, R Natrajan, A Mackay, FC Geyer, A Ashworth, JS Reis-Filho. Institut Claudius Regaud, Toulouse, France; ICR, London, United Kingdom
Background: Mucinous carcinomas have been shown to be transcriptionally distinct from invasive ductal carcinomas of no special type. Here we investigated if mucinous carcinomas would constitute a discrete molecular entity and defined the genomic aberrations that are characteristic of this special type of breast cancer.
Design: 17 mucinous breast carcinomas (12 pure and 5 mixed mucinous and invasive ductal carcinoma of no special type (IDC-NST)) were retrieved from our institutions' histopathology files. All cases were centrally reviewed for assessment of the type, histological grade, mitotic count and presence of a ductal carcinoma in situ. Immunohistochemical analysis was performed on a tissue microarray using a comprehensive panel of breast markers. Pure mucinous carcinomas were grade- and oestrogen receptor (ER) matched with IDCs-NST (n=24). Representative sections of the tumours were microdissected (in mixed tumours, each component was separately microdissected) and subjected to microarray-based comparative genomic hybridisation (aCGH) using a 32K BAC array platform.
Results: Mucinous carcinomas showed a relatively low level of genetic instability. Unsupervised hierarchical analysis showed that pure mucinous carcinomas were more homogeneous and preferentially clustered together (Fisher's exact test, p<0.001). Compared to grade- and ER-matched IDCs-NST, pure mucinous carcinomas significantly more frequently harboured gains in 1p36, 3p21, 4p16, 6p21, 7p22, 8q24, 9q34, 11p15, 11p11, 11q12-q13, 12q24, 16q22, 16q24, 17p13, 17q25, 18p11, 19p, 19q13, 22q13, and loss in 9q11 (Fisher's exact test adjusted p value <0.05). On the other hand, deletions of 16q were significantly less frequent in mucinous cancers. Although 11 pure mucinous carcinomas were of grade I or II, only 3 cases harboured 16q deletion. Finally, the IDC-NST and mucinous components of mixed cases displayed similar patterns of genetic aberrations and clustered together on unsupervised clustering analysis, however the IDC-NST component harboured more genomic alterations than the mucinous component.
Conclusions: Pure mucinous carcinomas are more homogeneous between themselves at the genetic level than IDCs-NST. In mixed mucinous tumours, the IDC-NST component displays a higher number of genomic changes, suggesting that in mixed cases it may evolve from the mucinous component.
Tuesday, March 23, 2010 9:00 AM
Platform Session: Section C, Tuesday Morning