HLA-G upregulation in pre-malignant and malignant lesions of the gastrointestinal tract

Donna E. Hansel, Ayman Rahman, Robb E. Wilentz, Ie Ming Shih, Michael T. McMaster, Charles J. Yeo, Anriban Maitra

Research output: Contribution to journalArticle

Abstract

HLA-G belongs to the nonclassical MHC class Ib group of molecules and has been implicated in mediating immune-responsiveness in various cancerous and non-cancerous cell types. We have examined HLA-G expression in a number of human gastrointestinal malignancies, including pancreatic ductal adenocarcinoma, ampullary cancer, biliary cancer, and colorectal cancer by immunolabeling analysis. We used indices of <5% (negative), 6-25%, 26-50%, 51-75%, and >75% (diffuse) to subclassify lesions based on percentage of positive cell labeling. Across all cancer subtypes, 52-79% of lesions demonstrated expression of HLA-G, with up to 33% of lesions demonstrating diffuse (>75%) expression. In addition, we utilized the neoplastic progression model of colorectal cancer to evaluate HLA-G protein expression in normal colon, tubulovillous adenomas, invasive cancer, and liver metastases arising from colorectal cancer. Focal HLA-G expression was detected in regions of normal colon adjacent to sites of adenomatous and cancerous lesions, as well as in all stages of cancer progression. Overall, the percentage of diffusely (>75%) labeled lesions appeared increased in preneoplastic and neoplastic conditions, as compared to normal colon. Specifically, tubulovillous adnenomas demonstrated pronounced diffuse labeling in 58% of lesions examined. No correlation with HLA-G expression and CD4+ or CD8+ T cells was identified. We propose that HLA-G expression is upregulated in a large percentage of gastrointestinal lesions and may serve to mediate immune-responsiveness in certain instances.

Original languageEnglish (US)
Pages (from-to)15-23
Number of pages9
JournalInternational Journal of Gastrointestinal Cancer
Volume35
Issue number1
StatePublished - Apr 18 2005

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Keywords

  • Ampullary cancer
  • Biliary cancer
  • Colon
  • Colorectal cancer
  • Gallbladder
  • Immune
  • Pancreas
  • Pancreatic cancer
  • Tolerance

ASJC Scopus subject areas

  • Oncology
  • Endocrinology
  • Gastroenterology

Cite this

Hansel, D. E., Rahman, A., Wilentz, R. E., Shih, I. M., McMaster, M. T., Yeo, C. J., & Maitra, A. (2005). HLA-G upregulation in pre-malignant and malignant lesions of the gastrointestinal tract. International Journal of Gastrointestinal Cancer, 35(1), 15-23.