1] Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea [2] Department of Pathology, SMG-SNU Boramae Medical Center, Seoul, South Korea.
Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
Mod Pathol. 2014 Mar;27(3):443-53. doi: 10.1038/modpathol.2013.160. Epub 2013 Sep 13.
It has been recently suggested that the expression levels of mutant HSP110 could be a prognostic marker in colorectal cancer with a high level of microsatellite instability (MSI-H). The aim of our study was to validate the prognostic significance of HSP110 mutation using immunohistochemistry and DNA testing in MSI-H colorectal cancer. Wild-type HSP110 (HSP110wt)-specific immunohistochemistry was performed in 168 MSI-H colorectal cancer tissues, and their expression levels were evaluated using a four-tier scoring system (0/1+/2+/3+). Of these tissues, 167 cases were analyzed for HSP110 T17 deletion. Associations with clinicopathological, molecular and survival parameters were statistically analyzed. The low-level expression of HSP110wt (0/1+) was observed in 40 MSI-H colorectal cancers (24%) and was significantly related to large HSP110 T17 deletions (≥ 4 bp, P<0.001). In survival analysis, patients with low HSP110wt expression (0/1+) showed better disease-free survival compared with those with high expression (2+/3+; P=0.005). This significance in survival difference was maintained in patients with 5-fluorouracil-based chemotherapy-treated tumors (P=0.024) and in those with stage III/IV tumors (P=0.032). Multivariate analysis confirmed the role of HSP110wt expression as an independent prognostic factor (P=0.016, hazard ratio=4.32). In MSI-H colorectal cancer, a low expression of HSP110wt is associated with large HSP110 T17 deletions and better clinical outcome. Immunohistochemistry of HSP110wt can be a simple and valuable tool for the prognostic and therapeutic stratification of patients with MSI-H colorectal cancer.
最近有人提出，突变 HSP110 的表达水平可能是微卫星不稳定（MSI-H）结直肠癌的预后标志物。我们的研究旨在通过免疫组织化学和 DNA 测试验证 HSP110 突变在 MSI-H 结直肠癌中的预后意义。在 168 例 MSI-H 结直肠癌组织中进行了野生型 HSP110（HSP110wt）特异性免疫组织化学检测，并使用四级评分系统（0/1+/2+/3+）评估其表达水平。在这些组织中，167 例分析了 HSP110 T17 缺失。统计分析了与临床病理、分子和生存参数的关联。HSP110wt 的低水平表达（0/1+）在 40 例 MSI-H 结直肠癌（24%）中观察到，与大的 HSP110 T17 缺失（≥4 bp，P<0.001）显著相关。在生存分析中，与 HSP110wt 高表达（2+/3+）相比，HSP110wt 低表达（0/1+）的患者无病生存更好（P=0.005）。在接受氟尿嘧啶为基础的化疗治疗的肿瘤患者（P=0.024）和 III/IV 期肿瘤患者（P=0.032）中，这种生存差异的意义仍然存在。多变量分析证实 HSP110wt 表达是独立的预后因素（P=0.016，危险比=4.32）。在 MSI-H 结直肠癌中，HSP110wt 的低表达与 HSP110 T17 大片段缺失相关，并且与更好的临床结局相关。HSP110wt 的免疫组织化学检测可以成为 MSI-H 结直肠癌患者预后和治疗分层的简单而有价值的工具。
