The expression and clinical significance of ribophorin II (RPN2) in human breast cancer.

ABSTRACT

Ribophorin II (RPN2), part of the N-oligosaccharyltransferase complex, is highly expressed in breast cancer stem cells and is associated with tumor metastasis through interaction with mutant p53. The clinicopathological implication of RPN2 expression is undetermined. We examined immunohistochemically the expression levels of RPN2 and p53 in primary breast cancer tissues surgically resected from 218 patients. The correlations of RPN2 expression with the intrinsic subtype defined by hormone receptors (HRs) and HER2, clinicopathological parameters, p53 expression, and patients' clinical outcomes were examined. RPN2 was positive in 139 (64%), and the incidence of RPN2 expression was higher in the triple-negative breast cancer (TNBC) (HR-/HER2-) (65%) and HER2-enriched (HR-/HER2+) subtype (95%) than in the luminal A-like (HR+/HER2-) subtype (58%) (P = 0.0009). RPN2 expression was also correlated with p53 nuclear accumulation (P = 0.04). The RPN2-positive/p53-positive patient group showed significantly poorer prognosis than the RPN2-negative group for disease-free survival (P = 0.05) and for overall survival (P = 0.02). By multivariate analyses, the combination of RPN2 and p53 was not an independent prognostic factor. RPN2 expression was correlated with clinically aggressive features of breast cancer. These data support the further clinical application of anti-RPN2 therapy and the development of personalized medicine.