Miura Yosuke, Kaira Kyoichi, Sakurai Reiko, Imai Hisao, Tomizawa Yoshio, Sunaga Noriaki, Minato Koichi, Hisada Takeshi, Oyama Tetsunari, Yamada Masanobu
Division of Respiratory Medicine, Gunma Prefectural Cancer Center, 617-1, Takahayashinishi-machi, Ota, Gunma, Japan.
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
Int J Clin Oncol. 2017 Oct;22(5):872-879. doi: 10.1007/s10147-017-1142-x. Epub 2017 May 26.
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.
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.
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.
Our findings indicate that the overexpression of GRP78/BiP is a novel predictor of favorable outcomes in patients with ATC who receive combination chemotherapy.
葡萄糖调节蛋白（GRP）78/免疫球蛋白重链结合蛋白（BiP）是内质网伴侣蛋白家族的一员，其在各类人类恶性肿瘤中的作用近来已得到研究。然而，GRP78/BiP在晚期胸腺癌（ATC）中的临床病理特征仍不清楚。我们旨在研究GRP78/BiP表达与ATC患者临床结局之间的关系。
1998年4月至2014年4月期间，在三家机构接受联合化疗的34例ATC患者纳入本研究。我们从他们的病历中回顾性收集患者特征，如治疗效果、病理结果和生存数据。我们进行免疫组织化学分析，以评估从手术切除或活检获得的肿瘤标本中GRP78/BiP的表达。
本研究包括21名男性（68%）和13名女性（32%），中位年龄为62岁（范围36 - 75岁）。65%的患者（34例中的22例）观察到GRP78/BiP过表达。GRP78/BiP表达与任何患者特征之间均无相关性。与低表达患者相比，GRP78/BiP高表达患者的总生存期（OS）显著更长（46.2个月对16.8个月，p = 0.04）。多变量分析表明，GRP78/BiP高表达是OS延长的独立预后因素。
我们的研究结果表明，GRP78/BiP过表达是接受联合化疗的ATC患者预后良好的新预测指标。
