Association of MHC class I expression and lymph node metastasis of gastric carcinoma

Hepatogastroenterology. 2013 May;60(123):611-5. doi: 10.5754/hge12433.

Abstract

Background/aims: HLA gene encodes MHC, which could represent a common mechanism for enhanced antitumor immune response through T-cell cytotoxicity. Loss of HLA class I expression has been considered to be an important prognostic factor in many malignancies. We investigated the impact of HLA class I expression on lymph node metastasis in gastric carcinoma.

Methodology: We examined HLA class I expression in clinical samples from 349 patients by immunohistochemistry and compared primary lesions and metastatic lymph nodes. We analyzed the expression of HLA class I antigen in gastric cancer cell lines using flow-cytometry and HLA-A typed these cell lines using PCR.

Results: HLA class I expression was down-regulated in metastatic lymph nodes compared with its expression in primary lesion. Patients with negative expression showed a significantly poorer prognosis. We observed down-regulation of HLA class I antigen in OCUM-2MLN cell line, which has a high potential for metastasizing to lymph node. PCR-SBT analysis indicated LOH of HLA-A gene in OCUM-2MLN.

Conclusions: We showed that HLA class I expression was abrogated in tumor cells that had metastasized to lymph nodes. We further suggest that loss of HLA class I due to LOH was associated with lymph node metastasis.

MeSH terms

  • Aged
  • Carcinoma / genetics
  • Carcinoma / immunology*
  • Carcinoma / mortality
  • Carcinoma / secondary*
  • Cell Line, Tumor
  • Chi-Square Distribution
  • Down-Regulation
  • Female
  • Flow Cytometry
  • HLA-A Antigens / genetics
  • HLA-A Antigens / metabolism*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Loss of Heterozygosity
  • Lymph Nodes / immunology*
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polymerase Chain Reaction
  • Prognosis
  • Proportional Hazards Models
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Time Factors

Substances

  • HLA-A Antigens