Abstract P2-11-18: Immunohistochemical expression of ubiquitin ligase CHIP (carboxyl terminus of Hsc70-interacting protein) as a significant prognostic marker in postmenopausal invasive breast cancer patients

Abstract

Abstract Background: CHIP is a U box type ubiquitin ligase that induces ubiquitination and degradation of its target proteins, which include several oncogenic proteins. We clarified that CHIP suppresses tumor growth and metastasis in human breast cancer by inhibiting oncogenic pathways (Nat Cell Biol 2009;11:312-9). In this study, we investigated the relationship between immunohistochemical CHIP expression and several biomarkers, and evaluated the correlation between CHIP expression and prognosis of patients with invasive breast cancer. Patients and Methods: In this study, 272 consecutive patients with invasive carcinoma of no special type with invasion >5 mm, treated in 2000-2001, were enrolled. We performed immunohistochemical staining with antibodies against CHIP, ER, PgR, and HER2. Cytoplasmic expression patterns of CHIP were scored as 0 (no stain), 1 (weak stain), 2 (moderate stain), and 3 (strong stain), and divided into high CHIP (score 3) and low CHIP (score 2, 1, 0) groups. We investigated the relationship between CHIP expression and ER, PgR, HER2, histological grade (HG) and lymph node status (pN). We also evaluated correlation between CHIP expression and prognosis (RFS) of patients. Results: CHIP expression was as follows: score 0, 49 patients (18.0%); score 1, 91 (33.5%); score 2, 83 (30.5%); score 3, 49 (18.0%). High CHIP correlated significantly with positive ER (p<0.001), positive PgR (P<0.001), negative HER2 (p = 0.02), and low HG (p = 0.01). RFS was relatively better in the high CHIP group (49 patients) than the low CHIP group (223 patients) (p = 0.09). In addition, in postmenopausal patients, RFS was significantly better in the high CHIP group (23 patients) than the low CHIP group (133 patients) (p = 0.04); this was not so in premenopausal cases (p = 0.68). Furthermore, RFS was significantly better in CHIP score 3 and ER positive cases (42 patients) than in CHIP score 0 and ER negative cases (34 patients) (p = 0.03). Conclusions: CHIP expression correlated with status of hormone receptors and HER2 and might be a potent prognostic factor in invasive breast cancer patients, especially postmenopausal cases. Immunohistochemical examination of CHIP is thought to be useful for evaluating prognosis of breast cancer patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-11-18.