Biological and prognostic relevance of mitogen-activated protein kinases in pancreatic adenocarcinoma.

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.

• Authors: Adriana Handra-Luca, Claude Lesty, Pascal Hammel, Alain Sauvanet, Vinciane Rebours, Antoine Martin, Remi Fagard, Jean-François Fléjou, Sandrine Faivre, Pierre Bédossa, Philippe Ruszniewski, Anne Couvelard
• Journal: Pancreas (Pancreas) Vol. 41 Issue 3 Pg. 416-21 (Apr 2012) ISSN: 1536-4828 [Electronic] United States
• PMID: 22158075 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Ki-67 Antigen
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• MAP Kinase Kinase 4
• MAP2K4 protein, human

Topics

• Adult
• Aged
• Biomarkers, Tumor (analysis)
• Carcinoma, Pancreatic Ductal (enzymology, mortality, secondary, surgery)
• Cell Proliferation
• Chi-Square Distribution
• Disease-Free Survival
• Female
• France
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Ki-67 Antigen (analysis)
• MAP Kinase Kinase 4 (analysis)
• Male
• Middle Aged
• Mitogen-Activated Protein Kinase 1 (analysis)
• Mitogen-Activated Protein Kinase 3 (analysis)
• Mitogen-Activated Protein Kinases (analysis)
• Multivariate Analysis
• Neoplasm Recurrence, Local
• Pancreatectomy
• Pancreatic Neoplasms (enzymology, mortality, pathology, surgery)
• Retrospective Studies
• Risk Assessment
• Risk Factors
• Time Factors
• Treatment Outcome
• p38 Mitogen-Activated Protein Kinases (analysis)