High expression of GRP78/BiP as a novel predictor of favorable outcomes in patients with advanced thymic carcinoma

• Published in: International journal of clinical oncology Vol. 22; no. 5; pp. 872 - 879
• Main Authors: Miura, Yosuke, Kaira, Kyoichi, Sakurai, Reiko, Imai, Hisao, Tomizawa, Yoshio, Sunaga, Noriaki, Minato, Koichi, Hisada, Takeshi, Oyama, Tetsunari, Yamada, Masanobu
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.10.2017; Springer Nature B.V
• Subjects: Adult; Aged; Binding sites; Biomarkers, Tumor - metabolism; Biopsy; Cancer; Cancer Research; Chemotherapy; Clinical outcomes; Endoplasmic reticulum; Female; Gene expression; Heat-Shock Proteins - metabolism; Humans; Immunohistochemistry; Male; Medical records; Medicine; Medicine & Public Health; Middle Aged; Multivariate analysis; Oncology; Original Article; Patients; Proteins; Surgical Oncology; Survival; Survival Analysis; Thymoma - drug therapy; Thymoma - metabolism; Thymoma - mortality; Thymus; Thymus Neoplasms - drug therapy; Thymus Neoplasms - metabolism; Thymus Neoplasms - mortality; Treatment Outcome; Prognostic factor; Biomarker; Glucose-regulated protein 78/immunoglobulin heavy chain binding protein; Thymic carcinoma; Endoplasmic reticulum stress
• ISSN: 1341-9625; 1437-7772
• DOI: 10.1007/s10147-017-1142-x

Background Glucose-regulated protein (GRP) 78/immunoglobulin heavy chain binding protein (BiP) is a member of the endoplasmic reticulum chaperone family, and its role in various types of human malignancies has recently been investigated. However, the clinicopathological characteristics of GRP78/BiP in advanced thymic carcinoma (ATC) remain unknown. We aimed to examine the relationship between GRP78/BiP expression and the clinical outcomes of ATC patients. Methods Thirty-four patients with ATC receiving combination chemotherapy at three institutions between April 1998 and April 2014 were enrolled in this study. We retrospectively collected patient characteristics such as therapeutic efficacy, pathological findings, and survival data from their medical records. We performed immunohistochemical analysis to evaluate the expression of GRP78/BiP in tumor specimens obtained from surgical resection or biopsy. Results This study included 21 men (68%) and 13 women (32%) with a median age of 62 years (range 36–75 years). GRP78/BiP overexpression was observed in 65% of the patients (22 of 34 patients). There was no correlation between GRP78/BiP expression and any patient characteristic. Patients with a high level of GRP78/BiP expression had significantly longer overall survival (OS) compared to those with a low level (46.2 vs. 16.8 months, p  = 0.04). Multivariate analysis demonstrated that a high level of GRP78/BiP expression was an independent prognostic factor for prolonged OS. Conclusions Our findings indicate that the overexpression of GRP78/BiP is a novel predictor of favorable outcomes in patients with ATC who receive combination chemotherapy.