Prognostic value of microsatellite instability in resectable pancreatic cancer

Clin Cancer Res. 2002 Aug;8(8):2536-40.

Abstract

The significance of microsatellite instability (MSI) as a prognostic predictor for resectable pancreatic cancer patients was examined. Forty-six histologically confirmed pancreatic cancer patients who had undergone resection were studied. DNA was extracted from the paraffin block sections by means of the microdissection method. PCR was performed using eight microsatellite primer marker sets. The mixed PCR sample was analyzed by a genetic analyzer. The number of MSI-positive patients was eight (17.4%) as determined by assessment of microsatellite variations in three or more of the eight tested markers. Univariate analysis revealed that patients with MSI-positive tumors had significantly longer survival times than patients with MSI-negative tumors, although there were no significant differences in clinicopathological factors between the two groups (median survival term, 62 months versus 10 months, respectively; P = 0.011). According to univariate survival analysis, patients with T3/T4, N1, or M1 tumors, as classified by Union Internationale Contre le Cancer staging, had significantly shorter survival times than patients with less progressive tumors. Multivariate survival analysis indicated that MSI status had an independent predictive value (hazard ratio = 5.577; P = 0.007). The tumor-infiltrating leukocyte intensity in MSI-positive tumors was significantly larger than that in MSI-negative tumors, suggesting that MSI-positive tumors may induce stronger antitumor immunity. In conclusion, a patient with MSI-positive pancreatic cancer may have a comparatively better prognosis after resection, possibly due to intensive immunoreaction to the tumor.

MeSH terms

  • Aged
  • CD3 Complex / biosynthesis
  • DNA / analysis
  • Disease-Free Survival
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Microsatellite Repeats*
  • Middle Aged
  • Multivariate Analysis
  • Mutation
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / surgery*
  • Polymerase Chain Reaction
  • Prognosis
  • Time Factors
  • Treatment Outcome

Substances

  • CD3 Complex
  • DNA