Low expression of junctional adhesion molecule A is associated with metastasis and poor survival in pancreatic cancer

Ann Surg Oncol. 2012 Dec;19(13):4330-6. doi: 10.1245/s10434-012-2381-8. Epub 2012 May 2.

Abstract

Background: Characterized by its highly aggressive tumor biology, pancreatic cancer still remains a fatal diagnosis. The junctional adhesion molecule A (JAM-A) is a type I transmembrane glycoprotein, which recently has been shown to affect the prognosis of several human malignancies.

Methods: JAM-A antigen expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumor tissue samples from a series (n = 186) of consecutive patients with pancreatic adenocarcinoma. Survival was calculated by Kaplan-Meier curves. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model.

Results: Low expression of JAM-A was observed in 79 (42 %) of 186 pancreatic cancer specimens and was significantly associated with poor overall survival (P < 0.01). By univariate analysis, low expression of JAM-A was found to correlate with positive lymph node status (P = 0.02), the presence of distant metastasis (P = 0.05), and tumor grade (P = 0.04), suggesting it may be an important event involved in cancer progression. Furthermore, in the subgroup of patients with surgically resected pancreatic cancer, low expression of JAM-A significantly correlated with decreased progression-free survival (P < 0.01). Multivariate analysis revealed JAM-A to be an independent predictor of poor outcome.

Discussion: These findings suggest for the first time that low levels of JAM-A expression in pancreatic cancer are associated with poor clinical outcome. JAM-A may represents a target molecule for functional inactivation and serve as a novel biomarker of adverse prognosis in pancreatic cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality*
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / mortality*
  • Carcinoma, Pancreatic Ductal / secondary
  • Case-Control Studies
  • Cell Adhesion Molecules / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / mortality*
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Receptors, Cell Surface / metabolism*
  • Retrospective Studies
  • Survival Rate

Substances

  • Cell Adhesion Molecules
  • F11R protein, human
  • Receptors, Cell Surface