Shiraishi Takehiro, Shinto Eiji, Yamadera Masato, Nagata Ken, Tsuda Hitoshi, Mochizuki Satsuki, Kajiwara Yoshiki, Okamoto Koichi, Einama Takahiro, Kishi Yoji, Ueno Hideki
Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359-0042, Japan.
Department of Basic Pathology, National Defense Medical College, Tokorozawa, Saitama 359-0042, Japan.
Oncotarget. 2020 Oct 27;11(43):3807-3817. doi: 10.18632/oncotarget.27774.
Mesothelin (MSLN) is a cell surface glycoprotein that is normally expressed in the mesothelial cells but highly expressed in several malignant tumors, where the high expression is generally associated with poor prognosis. In this work, 512 patients with stage III colorectal cancer (CRC) were examined to ascertain the prognostic value of MSLN expression in preoperative endoscopic biopsy specimens. MSLN expression was evaluated by immunohistochemical staining. The tumor cells were MSLN-positive in 61 of the 512 patients (11.9%). MSLN expression was associated with a shorter disease-specific survival (DSS) period (5-year DSS = 68.7%, = 0.0008). Besides, by multivariate analysis, MSLN expression was identified to be a marker of poor prognosis by multivariate analysis ( = 0.0033, hazard ratio (HR) = 2.31) as well as macroscopic type ( = 0.047, HR = 1.82) among the factors that can be evaluated preoperatively. MSLN-positive patients had a significantly poorer prognosis regardless of adjuvant chemotherapy administration ( = 0.0081 and = 0.0018 for surgery alone and chemotherapy, respectively). MSLN-positive patients in the adjuvant chemotherapy group exhibited a significantly lower risk of recurrence when compared with those in the surgery alone group ( = 0.0090). In conclusion, high MSLN expression observed in preoperative endoscopic biopsy specimens of stage III CRC was an independent poor prognostic factor. Preoperative evaluation of MSLN by immunohistochemical staining might be applied to select individuals for intensive preoperative chemotherapy among the stage III CRC patients.
间皮素（MSLN）是一种细胞表面糖蛋白，通常在间皮细胞中表达，但在几种恶性肿瘤中高度表达，其高表达通常与预后不良相关。在本研究中，对512例III期结直肠癌（CRC）患者进行检查，以确定术前内镜活检标本中MSLN表达的预后价值。通过免疫组织化学染色评估MSLN表达。512例患者中有61例（11.9%）的肿瘤细胞MSLN呈阳性。MSLN表达与较短的疾病特异性生存期（DSS）相关（5年DSS = 68.7%，P = 0.0008）。此外，多因素分析显示，在术前可评估的因素中，MSLN表达被确定为预后不良的标志物（P = 0.0033，风险比（HR）= 2.31）以及大体类型（P = 0.047，HR = 1.82）。无论是否进行辅助化疗，MSLN阳性患者的预后均明显较差（单纯手术组和化疗组的P分别为0.0081和0.0018）。与单纯手术组相比，辅助化疗组中的MSLN阳性患者复发风险显著降低（P = 0.0090）。总之，在III期CRC术前内镜活检标本中观察到的高MSLN表达是一个独立的不良预后因素。通过免疫组织化学染色对MSLN进行术前评估，可能有助于在III期CRC患者中选择接受强化术前化疗的个体。
