Cell polarity and cell adhesion associated gene expression differences between invasive micropapillary and no special type breast carcinomas and their prognostic significance

Abstract

AbstractInvasive micropapillary carcinoma of the breast (IMPC) has been in the focus of several studies given its specific histology and clinicopathological course. We analysed mRNA expression profiles and the prognostic value of 43 genes involved in cell polarity, cell-adhesion and epithelial–mesenchymal transition (EMT) in IMPC tumors and compared them to invasive breast carcinomas of no special type (IBC-NST). IMPCs (36 cases), IBC-NSTs (36 cases) and mixed IMPC-IBC NSTs (8 cases) were investigated. mRNA expression level of selected genes were analysed using the NanoString nCounter Analysis System. Distant metastases free survival (DMFS) intervals were determined. Statistical analysis was performed using Statistica 13.5 software. Twelve genes showed significantly different expression in the IMPC group. There was no difference in DMFS according to histological type (IBC-NST vs. IMPC). High CLDN3, PALS1 and low PAR6 expression levels in the entire cohort were associated with shorter DMFS, and PALS1 was proven to be grade independent prognostic factor. Positive lymph node status was associated with higher levels of AKT1 expression. Differences in gene expression in IMPC versus IBC-NST may contribute to the unique histological appearance of IMPCs. No marked differences were observed in DMFS of the two groups. Altered gene expression in the mTOR signaling pathway in both tumor subtypes highlights the potential benefit from AKT/mTOR inhibitors in IMPCs similarly to IBC-NSTs.