Striefler Jana Käthe, Riess Hanno, Lohneis Philipp, Bischoff Sven, Kurreck Annika, Modest Dominik Paul, Bahra Marcus, Oettle Helmut, Sinn Marianne, Bläker Henrik, Denkert Carsten, Stintzing Sebastian, Sinn Bruno Valentin, Pelzer Uwe
Department of Hematology, Oncology, and Tumor Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Faculty of Medicine and University Hospital Cologne, Institute of Pathology, University of Cologne, Cologne, Germany.
Front Oncol. 2021 Jul 27;11:670396. doi: 10.3389/fonc.2021.670396. eCollection 2021.
The Mucin-family protein, MUC1, impacts on carcinogenesis and tumor invasion. We evaluated the impact of MUC1 expression on outcome in a cohort of 158 patients with resected pancreatic ductal adenocarcinomas (PDAC) in the CONKO-001 study (adjuvant gemcitabine [gem] . observation [obs]).
The percentage of MUC1-positive tumor cells by immunohistochemistry (IHC) and the staining intensity were evaluated by two observers blinded to outcome. The numeric values of both parameters were multiplied, resulting in an immunoreactivity score (IRS) ranging from 0 to 12. The level of MUC1 expression was defined as follows: IRS 0-4 (low) IRS >4 (high). Outcomes in terms of disease-free (DFS) and overall survival (OS) were evaluated by Kaplan-Meier method, log-rank tests and Cox regressions.
In total, tumors of 158 study patients were eligible for immunohistochemistry of MUC1. High cytoplasmic MUC1 expression was associated with impaired DFS and OS in the overall study population (hazard ratio (HR) for DFS: 0.49, 95% CI 0.31 to 0.78, p = .003; HR for OS: 0.46, 95% CI 0.29 to 0.73, p = .001). In the study arms, prognostic effects of MUC1 were also evident in the observation group (HR for DFS: 0.55; 95% CI 0.29 to 1.04, p = .062; HR for OS: 0.34, 95% CI 0.17 to 0.67, p = .001) and trending in the gem group (HR for DFS: 0.48, 95% CI 0.24 to 0.95, p = .041; HR for OS: 0.56, 95% CI 0.28 to1.11, p = .093).
Our data suggest that MUC1 expression is a powerful prognostic marker in patients with PDAC after curatively intended resection.
黏蛋白家族蛋白MUC1对肿瘤发生和肿瘤侵袭有影响。在CONKO - 001研究(辅助吉西他滨[吉西]对比观察[观察])中,我们评估了158例接受胰腺导管腺癌(PDAC)切除术患者中MUC1表达对预后的影响。
由两名对结果不知情的观察者通过免疫组织化学(IHC)评估MUC1阳性肿瘤细胞的百分比和染色强度。将这两个参数的数值相乘,得出免疫反应评分(IRS),范围为0至12。MUC1表达水平定义如下:IRS 0 - 4(低),IRS>4(高)。采用Kaplan - Meier法、对数秩检验和Cox回归评估无病生存期(DFS)和总生存期(OS)方面的预后。
总共158例研究患者的肿瘤符合MUC1免疫组织化学检测条件。在整个研究人群中,高细胞质MUC1表达与DFS和OS受损相关(DFS的风险比[HR]:0.49,95%CI 0.31至0.78,p = 0.003;OS的HR:0.46,95%CI 0.29至0.73,p = 0.001)。在各研究组中,MUC1的预后影响在观察组中也很明显(DFS的HR:0.55;95%CI 0.29至1.04,p = 0.062;OS的HR:0.34,95%CI 0.17至0.67,p = 0.001),在吉西组中呈趋势(DFS的HR:0.48,95%CI 0.24至0.95,p = 0.041;OS的HR:0.56,95%CI 0.28至1.11,p = 0.093)。
我们的数据表明,MUC1表达是根治性切除术后PDAC患者的一个有力预后标志物。