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Biological and Prognostic Relevance of Mitogen-Activated Protein Kinases in Pancreatic Adenocarcinoma

2011; Lippincott Williams & Wilkins; Volume: 41; Issue: 3 Linguagem: Inglês

10.1097/mpa.0b013e318238379d

1536-4828

Adriana Handra‐Luca, Claude Lesty, Pascal Hammel, Alain Sauvanet, Vinciane Rebours, Antoine Martin, Rémi Fagard, Jean–François Fléjou, Sandrine Faivre, Pierre Bédossa, Philippe Ruszniewski, Anne Couvelard,

Cancer Genomics and Diagnostics

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.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.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).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.