Yosuke Miura1,2, Kyoichi Kaira3,4, Reiko Sakurai2,5, Hisao Imai1, Yoshio Tomizawa5, Noriaki Sunaga2,6, Koichi Minato1, Takeshi Hisada2, Tetsunari Oyama7, Masanobu Yamada2. 1. Division of Respiratory Medicine, Gunma Prefectural Cancer Center, 617-1, Takahayashinishi-machi, Ota, Gunma, Japan. 2. Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma, 371-8511, Japan. 3. Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma, 371-8511, Japan. kkaira1970@yahoo.co.jp. 4. Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. kkaira1970@yahoo.co.jp. 5. Division of Respiratory Medicine, National Hospital Organization Shibukawa Medical Center, 383, Shirai, Shibukawa, Gunma, Japan. 6. Oncology Center, Gunma University Hospital, Maebashi, Gunma, Japan. 7. Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Abstract
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.
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 humanmalignancies 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.
Entities:
Keywords:
Biomarker; Endoplasmic reticulum stress; Glucose-regulated protein 78/immunoglobulin heavy chain binding protein; Prognostic factor; Thymic carcinoma
Authors: Girum L Lemma; Ju-Whei Lee; Seena C Aisner; Corey J Langer; William J Tester; David H Johnson; Patrick J Loehrer Journal: J Clin Oncol Date: 2011-04-18 Impact factor: 44.544
Authors: K Kaira; M Toyoda; A Shimizu; H Imai; K Sakakura; O Nikkuni; M Suzuki; M Iijima; T Asao; K Chikamatsu Journal: Neoplasma Date: 2016 Impact factor: 2.575