This study provides insight into the biological specificities of invasive micropapillary carcinoma of the breast (IMPC), an entity characterized by cell polarity inversion and frequent lymphovascular invasion and axillary lymph node metastasis compared to invasive ductal carcinoma (IDC). Morphological review was combined with copy number analyses, genotyping (SNP6.0 Affymetrix), TP53 and PIK3CA sequencing and transcriptomic analysis in a series of 39 pure IMPC and the results were compared to those of 19 IDC with positive estrogen receptors, and positive axillary lymph node and lymphovascular invasion (ER+, N+, LVI+). The presence of numerous bi-nucleated cells was identified as a morphological pattern of IMPC. This specific trait was underlined by deregulation of the expression of genes involved in cell division. IMPC and IDC exhibit common genomic alterations including 8p-, 8q+, 16q-, 17p13- and 22q- and mutations of PIK3CA (10% for IMPC and 11% for IDC) and TP53 (13% in IMPC vs 33% in IDC). In contrast, IMPC were specifically characterized by frequent 17q23.2-q24.1 gains (54%), chromosomes 17q 23.1 (26%), 17q12 (22%), 8q22.1 (21%) amplifications and 6q16.1-q22.31 losses (43%). Within the IMPC group, unsupervised analysis of genomic data distinguished two distinct subsets: one subset (16 IMPC) exhibited a significant increase in 16p gains associated with near-diploid cells and the second subset (19 IMPC) characterized by a high frequency of 8q, 17q and 20q amplifications associated with near-tetraploid cells. This analysis showed that IMPC constitutes a distinct entity from ER+ N+ LVI+ IDC with, in particular, high frequencies of bi-nucleated cells, 17q gains and amplifications associated with 6q losses of heterozygosity. This study also showed that IMPC comprises two genomic subsets that may suggest the existence of different oncogenic mechanisms giving rise to the same morphological entity.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 87. doi:1538-7445.AM2012-87