Positive expression of L1-CAM is associated with perineural invasion and poor outcome in pancreatic ductal adenocarcinoma

Ann Surg Oncol. 2010 Aug;17(8):2213-21. doi: 10.1245/s10434-010-0955-x. Epub 2010 Feb 17.

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) frequently invades and migrates along neural tissue, which results in local tumor recurrences, distant metastases, and poor prognosis. We evaluated whether L1 cell adhesion molecule (L1-CAM) and glial cell line-derived neurotrophic factor (GDNF) expression in PDAC correlated with neural invasion and overall survival on a large cohort of previously untreated patients.

Methods: L1-CAM and GDNF were examined by immunohistochemistry in pancreatic cancer tissue samples of 94 cases with PDAC on a tissue microarray. The molecular findings were correlated with pain, clinicopathologic characteristics, and overall survival in these patients.

Results: L1-CAM and GDNF were overexpressed in pancreatic cancer tissues compared with the adjacent normal tissues of pancreas. Positive L1-CAM expression was associated with node involvement (P = 0.007), vascular invasion (P = 0.012), perineural invasion (P = 0.001), and higher degree of pain (P = 0.005). In univariate analysis, tissue expression of L1-CAM was associated with poor survival (hazard ratio, 2.508; 95% confidence interval, 1.551-4.053; P < 0.001), and this was also significant in multivariate analysis (hazard ratio, 2.046; 95% confidence interval, 1.200-3.488; P = 0.009). Positive staining of GDNF, neural invasion, and vascular invasion were all statistically significantly related to unfavorable prognosis.

Conclusions: Enhanced expression of L1-CAM may contribute to the pain syndrome and perineural invasion and may correlate with poor overall survival in human pancreatic cancer.

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Carcinoma, Pancreatic Ductal* / metabolism
  • Carcinoma, Pancreatic Ductal* / mortality
  • Carcinoma, Pancreatic Ductal* / pathology
  • Female
  • Follow-Up Studies
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Proteins / metabolism*
  • Neural Cell Adhesion Molecule L1 / metabolism*
  • Pain Measurement
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / mortality
  • Pancreatic Neoplasms* / pathology
  • Peripheral Nerves / pathology*
  • Prognosis
  • Survival Rate

Substances

  • Glial Cell Line-Derived Neurotrophic Factor
  • Neoplasm Proteins
  • Neural Cell Adhesion Molecule L1