title: HLA-G upregulation in pre-malignant and malignant lesions of the gastrointestinal tract.
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.
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Donna E
authors.initials: DE
authors.lastname: Hansel
authors.forename: Ayman
authors.initials: A
authors.lastname: Rahman
authors.forename: Robb E
authors.initials: RE
authors.lastname: Wilentz
authors.forename: Ie-ming
authors.initials: IeM
authors.lastname: Shih
authors.forename: Michael T
authors.initials: MT
authors.lastname: McMaster
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018450:Disease Progression; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D020869:Gene Expression Profiling; D006680:HLA Antigens / Q000096:biosynthesis* / Q000502:physiology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000502:physiology*; D006801:Humans; D007118:Immunoassay; D011230:Precancerous Conditions / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I
references.citation: J Immunol. 2001 Apr 15;166(8):5018-26
references.pmid: 11290782
references.citation: Trends Immunol. 2003 Feb;24(2):82-7
references.pmid: 12547505
references.citation: Clin Cancer Res. 2003 Oct 1;9(12):4460-4
references.pmid: 14555519
references.citation: Hum Immunol. 1994 Sep;41(1):79-86
references.pmid: 7836069
references.citation: Tissue Antigens. 1999 Apr;53(4 Pt 1):335-46
references.pmid: 10323337
references.citation: Immunogenetics. 2003 Feb;54(11):767-75
references.pmid: 12618909
references.citation: Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4510-5
references.pmid: 9539768
references.citation: Hum Immunol. 2000 Nov;61(11):1138-49
references.pmid: 11137219
references.citation: Trends Immunol. 2001 Oct;22(10):553-5
references.pmid: 11574278
references.citation: Transplant Proc. 2001 May;33(3):2355-9
references.pmid: 11377558
references.citation: Blood. 2002 Jan 15;99(2):609-17
references.pmid: 11781245
references.citation: Int J Mol Med. 1998 Sep;2(3):349-51
references.pmid: 9855710
references.citation: J Immunol. 2000 Jun 15;164(12):6100-4
references.pmid: 10843658
references.citation: J Reprod Immunol. 2000 Aug;48(1):17-26
references.pmid: 10996380
references.citation: Am J Surg Pathol. 2002 Jul;26(7):914-20
references.pmid: 12131159
references.citation: Eur J Immunol. 2003 Jan;33(1):125-34
references.pmid: 12594841
references.citation: J Immunol. 2002 May 1;168(9):4772-80
references.pmid: 11971028
references.citation: Immunol Today. 2000 Nov;21(11):532-4
references.pmid: 11186460
references.citation: Am J Pathol. 2002 Nov;161(5):1541-7
references.pmid: 12414502
references.citation: J Reprod Immunol. 1999 Jul;43(2):203-11
references.pmid: 10479056
references.citation: Eur J Immunogenet. 1996 Aug;23(4):311-20
references.pmid: 8858287
references.citation: Am J Pathol. 2001 Sep;159(3):817-24
references.pmid: 11549573
references.citation: Immunol Rev. 1998 Jun;163:129-38
references.pmid: 9700506