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  • Title: Biological and prognostic relevance of mitogen-activated protein kinases in pancreatic adenocarcinoma.
    Author: Handra-Luca A, Lesty C, Hammel P, Sauvanet A, Rebours V, Martin A, Fagard R, Fléjou JF, Faivre S, Bédossa P, Ruszniewski P, Couvelard A.
    Journal: Pancreas; 2012 Apr; 41(3):416-21. PubMed ID: 22158075.
    Abstract:
    OBJECTIVES: The aims of this study were to study the biological and clinical significance of 3 main proteins of the mitogen-activated protein kinase (MAPK) signaling pathway, ERK1/2, P38, and MKK4, in a series of patients having pancreatic adenocarcinomas treated by surgery. METHODS: We examined the immunohistochemical expression of 3 MAPK proteins, ERK1/2, P38, and MKK4 in 99 surgically resected pancreatic ductal adenocarcinomas. Tumor protein expression was studied with regard to pathological characteristics and to postsurgical recurrence-free and overall survivals. RESULTS: MKK4 expression was related to tumor cell proliferation, evaluated by the Ki67 index (P < 0.01). ERK1/2 expression was related to a shorter recurrence-free survival on both univariate and multivariate analysis (P < 0.01; odds ratio, 8.39; 95% confidence interval, 2.68-26.26) independently of lymph node metastases and tumor size, and to a shorter overall survival (P = 0.01) on univariate analysis. In patients without postsurgical treatment, both ERK1/2 and P38 tumor expression correlated with a shorter recurrence-free survival (P < 0.01 and P = 0.02, respectively). CONCLUSIONS: The results of our study suggest that in pancreatic ductal adenocarcinomas, the MKK4 protein was directly related to high cell proliferation, and that tumor ERK1/2 and P38 expression correlated to shorter postsurgical recurrence-free and overall survivals.
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