Abstract P4-04-04: Polarity Abnormalities in Invasive Carcinomas of the Breast: Analysis of Invasive Micropapillary Carcinoma of the Breast

Abstract

Abstract Aims: Invasive micropapillary carcinomas (IMPC) are rare (<2% of all invasive breast carcinomas) and characterized by clusters of cells with an inverted polarity surrounded by a clear space that separate them from the extracellular matrix. These tumors harbor vascular invasion and axillary lymph node involvement in more than 70% of the cases. We performed a detailed analysis of cellular polarity in a series of 25 IMPC to get insight in the putative role of proteins involved in the maintenance of cellular polarity in that carcinoma subtype. Methods: Polarity analysis has been performed by immunohistochemistry on a tissue-micro-array of a series of twenty-five invasive micropapillary carcinomas. Apical (p-ERM, a marker of phosphorylated ezrin, moesin and radixin, aPKCz, MUC1 and GM130, a marker of the golgi apparatus), basal (collagen IV), or baso-lateral (EGFR, E-cadherin, b-catenin and ERBB2) markers were assessed. Results: Apical markers MUC1, aPKCz, P-ERM were expressed at the external cellular pole in 88% (22/25), 60% (15/25) and 40% (10/25) of the cases respectively. Notably, 15/25 (60%) were p-ERM negative. Twenty-four cases/25 (96%) demonstrated a GM130 localisation at the external pole of the cells, with an abnormal internal and external localisation of the labelling in 15/24 positive cases (62%). Finally, 24% (6/25) cases presented all these apical markers located at the external part of the cells and 92% (23/25) had at least one of the apical markers in external position. The large majority of the cases (96%; 24/25) demonstrated no collagen IV labelling at the external part of the cell clusters. Intercellular junction proteins E-cadherin and b-catenin were expressed in all cases with a complete absence of staining at the apical inverted pole for both markers. Interestingly, a thick and strong labelling was observed for E-cadherin and for b-catenin in 36% (9/25) and 92% (23/25) of the cases respectively. EGFR was negative in 24 out of the 25 cases (96%). In contrast, ERBB2 was overexpressed in 6/25 (24%) of cases with a membranous ERBB2 labelling except external at the inverted apical pole. EGFR and ERBB2 are considered in normal cells as a baso-lateral marker. Conclusion: IMPC present a clear inverted apical pole MUC-1 and/or aPKCz and/or phospho-ERM positive with the golgi apparatus facing the external membrane of cell clusters, oriented towards the clear space and the extracellular matrix. The intercellular junctions in IMPC are abnormal with a thick E-cadherin and b-catenin labelling compared to normal cells. These abnormal cell orientation and junctions could be a consequence of molecular alterations that are currently being analysed in our laboratory, and that could explain the high frequency of loco-regional lymphatic tumor extension observed in IMPC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-04-04.