title: 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.
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.|Department of Basic Pathology, National Defense Medical College, Saitama, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.affiliation: Department of Basic Pathology, National Defense Medical College, Saitama, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Takeshita
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Ryou-U
authors.initials: RU
authors.lastname: Takahashi
authors.affiliation: Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Tamura
authors.affiliation: Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Sadako
authors.initials: S
authors.lastname: Akashi-Tanaka
authors.affiliation: Department of Surgery, National Defense Medical College, Saitama, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Moriya
authors.affiliation: Department of Surgery, National Defense Medical College, Saitama, Japan.
authors.forename: Tamio
authors.initials: T
authors.lastname: Yamasaki
authors.affiliation: Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Department of Surgery, National Defense Medical College, Saitama, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Yamamoto
authors.affiliation: Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochiya
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D018567:Breast Neoplasms, Male / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006602:Hexosyltransferases / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D006602:Hexosyltransferases; C517590:RPN2 protein, human; D046988:Proteasome Endopeptidase Complex
keywords: breast cancer; cancer stem cell; p53; ribophorin II