Expression of ROR1 has prognostic significance in triple negative breast cancer

Abstract

Overexpression of receptor tyrosine kinase-like orphan receptor (ROR1) in a variety of human malignancies is associated with aggressive behaviour. Therapeutic agents targeting ROR1 have shown promising results in vivo and in vitro studies. In breast cancer, high-level expression of ROR1 mRNA is associated with high-grade tumours and metastasis. We investigated the prevalence and prognostic significance of ROR1 expression in triple negative breast cancer (TNBC). ROR1 was immunohistochemically stained on full-face sections of 210 TNBC patient samples. Forty-seven TNBC cases (22.4 %) showed strong ROR1 expression, which was associated with shorter disease-free survival (DFS; P = 0.00015), distant metastasis-free survival (DMFS; P = 0.00013) and overall survival (OS; P = 0.026) in univariate analyses. Results were confirmed by multivariate analysis. Seventy TNBC cases (33.3 %) with medullary features showed longer OS (P = 0.00013). We divided the whole series into two subgroups based on the presence or absence of medullary features. Strong ROR1 expression retained a predictive value of shorter DFS and DMFS in both subgroups. Our study suggests that strong ROR1 expression might be an independent adverse prognostic factor in TNBC patients and may serve as a potential marker for patient selection in ROR1-targeted therapy. More large-scale studies are needed to clarify its potential usefulness.

Keywords: Carcinoma with medullary features; Prognosis; ROR1 tyrosine kinase; Triple negative breast cancer.