Kim Seok-Hyun, Ji Jun Ho, Park Kyung Tae, Lee Ji Hyun, Kang Kyung Woo, Park Jae Hong, Hwang Sang Won, Lee Eun Hee, Cho Yu Ji, Jeong Yi Yeong, Kim Ho-Cheol, Lee Jong Deog, Jang Inseok, Lee Jong Sil, Lee Hyoun Wook, Lee Gyeong-Won
Division of Haematology and Medical Oncology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
Division of Pulmonology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
Histopathology. 2015 Oct;67(4):509-19. doi: 10.1111/his.12675. Epub 2015 Mar 26.
The aim of this study was to investigate the expression of Hsp90β and GRP94, and elucidate the clinical significance of their expression, in patients with resectable non-small-cell lung cancer (NSCLC).
Surgical tissue specimens were obtained from 208 patients with NSCLC who underwent surgical resection. The expression levels of Hsp90β and GRP94 were assessed with tissue microarrays and immunohistochemistry. No correlations were observed between Hsp90β or GRP94 expression and several clinicopathological factors. The high-Hsp90β group [median overall survival (OS) 20.4 months; 95% confidence interval (CI) 0.000-40.864] showed a significant decrease in OS as compared with the low-Hsp90β group (median OS not reached; P = 0.003). In contrast to the Hsp90β analysis, the GRP94 analysis did not show a difference in OS. Moreover, in subgroup analyses of patients with squamous cell carcinoma histology, OS (P = 0.012) and relapse-free survival (P = 0.044) were significantly worse in the high-Hsp90β group than in the low-Hsp90β group. Multivariate analysis suggested that old age [hazard ratio (HR) 1.568; 95% CI 1.019-2.412; P = 0.041], advanced disease (HR 2.066; 95% CI 1.218-3.502; P = 0.007) and high Hsp90β expression (HR 1.802; 95% CI 1.061-3.060; P = 0.029) were independent poor prognostic factors for OS.
Hsp90β expression might be a useful marker of poor OS, although further large prospective studies are warranted to validate our findings.
本研究旨在调查可切除的非小细胞肺癌（NSCLC）患者中热休克蛋白90β（Hsp90β）和葡萄糖调节蛋白94（GRP94）的表达情况，并阐明其表达的临床意义。
从208例行手术切除的NSCLC患者中获取手术组织标本。采用组织芯片和免疫组织化学方法评估Hsp90β和GRP94的表达水平。未观察到Hsp90β或GRP94表达与多个临床病理因素之间存在相关性。高Hsp90β组（中位总生存期[OS] 20.4个月；95%置信区间[CI] 0.000 - 40.864）与低Hsp90β组（中位OS未达到；P = 0.003）相比，OS显著降低。与Hsp90β分析不同，GRP94分析未显示OS存在差异。此外，在鳞状细胞癌组织学患者的亚组分析中，高Hsp90β组的OS（P = 0.012）和无复发生存期（P = 0.044）显著差于低Hsp90β组。多因素分析表明，高龄（风险比[HR] 1.568；95% CI 1.019 - 2.412；P = 0.041）、疾病进展（HR 2.066；95% CI 1.218 - 3.五02；P = 0.007）和高Hsp90β表达（HR 1.802；95% CI 1.061 - 3.060；P = 0.029）是OS的独立不良预后因素。
Hsp90β表达可能是OS不良的一个有用标志物，尽管需要进一步开展大型前瞻性研究来验证我们的发现。
