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Epithelial-Mesenchymal Transition (EMT) and Activated Extracellular Signal-regulated Kinase (p-Erk) in Surgically Resected Pancreatic Cancer

¹ Department of Gastrointestinal Medical Oncology, UT-MD Anderson Cancer Center, Unit 426, 1515 Holcombe Ave, Houston, TX 77030, USA
² Departments of Surgery, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY 14263, USA
³ OSI Pharmaceuticals, 41 Pinelawn Road, Melville, NY 11747, USA
⁴ Biostatistics, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY 14263, USA
⁵ Pharmacology, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY 14263, USA
⁶ Pathology, UT-MD Anderson Cancer Center, Unit 426, 1515 Holcombe Ave, Houston, TX 77030, USA
⁷ Pathology, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY 14263, USA

Correspondence: Address correspondence and reprint requests to: M. M. Javle; E-mail: mjavle{at}mdanderson.org

Background: EMT or transformation to the mesenchymal phenotype plays an important role in tumor invasion and metastasis. In vitro data suggest that mesenchymal transformation may correlate with the activation of PI3 kinase and Ras/Erk pathways. We investigated the expression of EMT markers (low E-cadherin, high fibronectin, and vimentin) and their association with p-Erk in resected pancreatic cancer.

Methods: Clinical data/surgical specimens from 34 consecutive pancreatic cancer patients (pts) who underwent pancreatectomy were included. Immunohistochemical staining was performed on formalin-fixed paraffin-embedded tissues using monoclonal antibodies against vimentin, fibronectin, E-cadherin, and p-Erk. The results were correlated with clinicopathological parameters and survival. Survival analysis (log-rank test, Cox proportional hazard model), categorical data analysis (Pearson’s chi-square, Fisher’s exact test) and Kendall’s tau were performed at a significance level of 0.05.

Results: The patient population was formed from 13 males and 21 females, with a median age of 66 years (range 38–84 years); American Joint Committee on Cancer (AJCC) stage 1 (n = 2), 2 (n = 27), 3 (n = 5); histological grade 1 (n = 4), 2 (n = 13), 3 (n = 16), 4 (n = 1). Median survival was 15 months (95% CI: 11–24 months). Fibronectin overexpression correlated with the presence of vimentin (p = 0.0048) and activated Erk (p = 0.0264). There was a borderline association of fibronectin with worsening grade (p = 0.06). A negative association between vimentin and E-cadherin was noted (p = 0.0024). Increased fibronectin or vimentin and decreased E-cadherin correlated with poor survival.

Conclusion: EMT is associated with poor survival in surgically resected pancreatic adenocarcinoma. A correlation between activated Erk and fibronectin was identified that may open avenues for targeted therapy for this subgroup.

Key Words: Pancreatic neoplasms • Cell transformation-neoplastic • Mitogen-activated protein kinases

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