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

  • Gastrointestinal Oncology
  • Original Papers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

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.

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ACKNOWLEDGEMENTS

We would like to acknowledge OSI pharmaceuticals for research support; Donna Olesczek for immunostaining procedures; and Drs. Sreeram Maddipatla,Victor Yosuico and Eiad Nasser for clinical contribution.

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Authors and Affiliations

  1. Department of Gastrointestinal Medical Oncology, UT-MD Anderson Cancer Center, Unit 426, 1515 Holcombe Ave, Houston, TX, 77030, USA

    M. M. Javle MD

  2. Departments of Surgery, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY, 14263, USA

    J. F. Gibbs MD

  3. OSI Pharmaceuticals, 41 Pinelawn Road, Melville, NY, 11747, USA

    K. K. Iwata PhD & P. Rutledge MA, MBA

  4. Biostatistics, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY, 14263, USA

    Y. Pak PhD & J. Yu PhD

  5. Pharmacology, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY, 14263, USA

    J. D. Black PhD

  6. Pathology, UT-MD Anderson Cancer Center, Unit 426, 1515 Holcombe Ave, Houston, TX, 77030, USA

    D. Tan MD

  7. Pathology, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY, 14263, USA

    T. Khoury MD

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  1. M. M. Javle MD
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  2. J. F. Gibbs MD
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Correspondence to M. M. Javle MD.

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Javle, M.M., Gibbs, J.F., Iwata, K.K. et al. Epithelial-Mesenchymal Transition (EMT) and Activated Extracellular Signal-regulated Kinase (p-Erk) in Surgically Resected Pancreatic Cancer. Ann Surg Oncol 14, 3527–3533 (2007). https://doi.org/10.1245/s10434-007-9540-3

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  • DOI: https://doi.org/10.1245/s10434-007-9540-3

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