Abstract
BackgroundThe 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] vs. observation [obs]).MethodsThe 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) vs 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.ResultsIn 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).ConclusionOur data suggest that MUC1 expression is a powerful prognostic marker in patients with PDAC after curatively intended resection.
Highlights
Pancreatic CancerAdjuvant chemotherapy is standard of care (SOC) in patients with pancreatic ductal adenocarcinomas (PDAC) after R0/R1 resection of the primary tumor with curative intent
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
High cytoplasmic MUC1 expression was associated with impaired disease-free survival (DFS) and overall survival (OS) in the overall study population (hazard ratio (HR) for DFS: 0.49, 95% 95% confidence interval (CI) 0.31 to 0.78, p = .003; HR for OS: 0.46, 95% CI 0.29 to 0.73, p = .001)
Summary
Adjuvant chemotherapy is standard of care (SOC) in patients with PDAC after R0/R1 resection of the primary tumor with curative intent. The transmembrane mucin glycoprotein Mucin-1 (MUC1), known as CA 15-3, is a member of the mucin family of proteins expressed at the apical surface of epithelial cells. MUC1 positive carcinomas are associated with a hyperactivation of critical signaling pathways such as mitogenactivated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K/Akt) and wingless type (Wnt) pathway [5]. 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] vs observation [obs])
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