Immunohistochemistry and molecular detection of nodal micrometastases in pancreatic cancer

J Surg Res. 2001 Feb;95(2):141-6. doi: 10.1006/jsre.2000.6026.

Abstract

Purpose: Assays based on polymerase chain reaction (PCR) demonstrate mutated Kiras in the regional nodes of a majority of patients with node-negative stage I or II (T(1-3), N(0), M(0)) pancreatic adenocarcinoma. The hypothesis that the presence of mutated Kiras equates with micrometastases has not been validated by detailed histologic examination nor has an impact on survival been demonstrated.

Methods: We examined the paraffin blocks of the primary tumor and regional lymph nodes from all 30 patients from 1984 to 1998 with resected pN(0) stage I or II pancreatic adenocarcinoma. DNA was analyzed for mutations in codon 12 of the Kiras oncogene by PCR and restriction digest with BstN1 (RFLP). All nodes were examined by histology of 4 hematoxylin and eosin-stained step sections and immunohistochemistry (HPE/IHC) with AE3/AE1 epithelial cell marker antibody.

Results: Examination of the regional lymph nodes of the 30 patients demonstrated nodal metastases in 9 (30%) by step-section histology alone, 14 (46.7%) by HPE/IHC, 19 (63.3%) by PCR/RFLP, and 25 (83.3%) by a combination of PCR/RFLP and HPE/IHC. Seven cases were HPE/IHC positive yet PCR/RFLP negative while 10 cases were PCR/RFLP positive and HPE/IHC negative. Median survival (months) did not differ if nodes were negative or positive by HPE/IHC (20.5 vs 17.5) or PCR/RFLP (20.0 vs 19.0) or a combination of these techniques (25 vs 18.5).

Conclusions: A great majority (83.3%) of patients with pathologic stage I or II pancreatic cancer had metastases in their regional nodes. Step-sectioning with immunohistochemistry and PCR/RFLP are complementary tests in detection of metastatic cancer cells. Nodal micrometastases did not adversely influence survival.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Aged
  • Codon
  • Female
  • Genes, ras*
  • Humans
  • Immunohistochemistry / methods
  • Lymphatic Metastasis / pathology
  • Male
  • Mutation*
  • Neoplasm Staging
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Reproducibility of Results
  • Retrospective Studies
  • Survival Analysis

Substances

  • Codon