Molecular Analysis of Invasive Micropapillary Carcinoma of the Breast
N Gruel, V Raynal, P Freneaux, C Lucchesi, R Karkouche, G Pierron, V Fourchotte, Y Kirova, JY Pierga, X Sastre-Garau, B Sigal-Zafrani, S Roman-Roman, O Delattre, A Vincent-Salomon. INSERM U830, Paris, France; Institut Curie, Paris, France
Background: Invasive micropapillary carcinoma (IMPC) of the breast is a rare entity, associated with frequent axillary lymph node metastasis and vascular invasion and has recently been identified as being luminal.
Design: To get insight the molecular alterations of IMPC, we performed array CGH and transcriptomic (Affymetrix U133 2+) analyses of 25 IMPC and compared them with 25 cases of estrogens positive invasive ductal carcinomas (IDC), all with vascular (LVI) and axillary lymph node invasion (N+). An immunohistochemistry analysis was performed with antibodies against estrogens (ER) and progesterone (PR), ERBB2, MUC1 and E-cadherin.
Results: The majority of IMPC was N+ (69%), LVI+ (84%), grade 2 (64%), ER positive (92%), and were ERBB2 positive in 6/25 cases (24%). All cases demonstrated an inverted apical pole MUC1 positive/E-cadherin negative. IDC were all N+, LVI + and ER +, in majority grade 2 (15/25 cases 60%) and 2 cases were ERBB2 3+ (8%). Genomic analyses showed that both groups shared gains of 1q, 8q24, 16p and 20q and losses of 16q (observed in up to 18/25 (72%) of IMPC cases). Interestingly, a specific genomic signature of IMPC was defined by significantly more frequent gains of 8p12-q24 and 17q23-q24 regions, and losses located on chromosomes 8pter-p12, 13q12-q34 and 22q. Fifty-three regions of high level amplifications were found in 64% (16 /25 cases) of IMPC and IDC cases, respectively. Four regions of amplifications were preferentially observed in IMPC: 2 on chromosome 8 (8q12.1 and 8q21.13), one on chromosome 16p13.3 (CCNF gene) and one on chromosome 17q22 (BCAS3 gene). Unsupervised analysis of transcriptomic data showed that IMPC and LVI+ N+ IDC clustered in groups according to their genomic status rather than according to their histological type. However, supervised analyses of transcriptomic data from the IMPC and LVI+ N+ IDC showed that genes involved in cell-matrix adhesion or cytoskeleton organization were differentially expressed between the two groups.
Conclusions: IMPC are luminal carcinomas characterized by recurrent amplicons (8q, 16p and 17q) and a genomic signature associating 8p losses/8q gains and 16p gains/16q losses combination with 17q23-24 gains, 13q and 22q losses. Transcriptomic analyses identified genes of interest involved in cell-matrix adhesion and cytoskeleton organization that could lead to the identification of new therapeutic targets in IMPC.
Tuesday, March 10, 2009 8:00 AM
Platform Session: Section B, Tuesday Morning