title: Prognostic value of the ubiquitin ligase carboxyl terminus of the Hsc70-interacting protein in postmenopausal breast cancer.
abstract: The carboxyl terminus of the Hsc70-interacting protein (CHIP) is considered to induce the ubiquitination and degradation of several oncogenic proteins, and play a role in the inhibition of tumor progression and invasion under experimental conditions. However, the impact of CHIP expression on the prognosis of breast cancer patients has not yet been established. In this study, using an immunohistochemical method, 272 patients with invasive breast cancer were assessed for the expression of CHIP (graded scores 0-3) and the statuses of biomarkers, such as estrogen receptor (ER), progesterone receptor (PgR), and HER2. The relationships between the statuses of CHIP and biomarkers as well as clinical features were also evaluated, and that between the expression of CHIP and patient prognosis was analyzed. We revealed that the strong expression of CHIP correlated with positive ER (P < 0.001), positive PgR (P < 0.001), and negative HER2 (P = 0.02). In postmenopausal patients, relapse-free survival (RFS) was significantly better in the high CHIP group than in the low CHIP group (P = 0.042). In addition, RFS and cancer-specific survival (CSS) were significantly better in patients with ER-positive/CHIP score 3 tumors than in those with ER-negative/CHIP score 0 tumors (RFS: P = 0.038, CSS: P = 0.0098). The methylation status of CHIP gene promoter did not always account for the down-regulation of its expression. In conclusion, the overexpression of CHIP is a potent prognostic factor of a good prognosis in ER-positive breast cancer patients in the postmenopausal phase.
authors.affiliation: Division of Breast Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan.|Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Gunma, Japan.
authors.forename: Sasagu
authors.initials: S
authors.lastname: Kurozumi
authors.affiliation: Research Institute for Clinical Oncology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Department of Molecular and Functional Dynamics, Tohoku University, 2-1 Seiryo-chou, Aoba-ku, Sendai, 980-8575, Miyagi, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Ibaraki, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hiyoshi
authors.affiliation: Research Institute for Clinical Oncology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Suda
authors.affiliation: Department of Molecular and Functional Dynamics, Tohoku University, 2-1 Seiryo-chou, Aoba-ku, Sendai, 980-8575, Miyagi, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Gohno
authors.affiliation: Division of Breast Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Division of Breast Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takei
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Gunma, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Horiguchi
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Gunma, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Takeyoshi
authors.affiliation: Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Gunma, Japan.
authors.forename: Tetsunari
authors.initials: T
authors.lastname: Oyama
authors.affiliation: Department of Pathology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kurosumi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008408:Mastectomy / Q000379:methods; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D017698:Postmenopause; D011379:Prognosis; D011401:Promoter Regions, Genetic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D044767:Ubiquitin-Protein Ligases; C467728:STUB1 protein, human; C508053:ERBB2 protein, human
keywords: Breast cancer; carboxyl terminus of the Hsc70-interacting protein (CHIP); postmenopausal patients; prognostic factor