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. 1988 Apr;57(4):369–373. doi: 10.1038/bjc.1988.84

HLA expression in human hepatocellular carcinoma.

A C Paterson 1, R Sciot 1, M C Kew 1, F Callea 1, G M Dusheiko 1, V J Desmet 1
PMCID: PMC2246568  PMID: 2839219

Abstract

This study examines the expression of MHC class I and II antigens and their related invariant chains in 70 cases of human hepatocellular carcinoma (HCC), using monoclonal (Mabs) and polyclonal antibodies. In comparison with normal hepatocytes, the majority (94.3%) of HCCs show enhancement or acquisition of HLA-A, B, C in either a cytoplasmic or membranous distribution, with staining being uniformly distributed throughout the specimen. HLA-A, B, C was accompanied by beta 2-microglobulin expression in all but two cases. Although 44.9% of specimens showed HLA-DR expression, positively staining tumour cells were often sparse and heterogeneously distributed. By contrast, the invariant (I) chain, present in 47.1% of cases, was frequently intensively stained and extensive in distribution. HLA-DR staining was usually cytoplasmic although two cases showed faint membranous enhancement. In addition to HLA-DR and I-chain, two cases also showed HLA-DQ staining. Display of MHC antigens was not related to tumour differentiation or size of the lesion (resected vs. advanced tumours). It is possible that the acquisition of class I antigens by the majority of HCCs may influence tumour behaviour.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cresswell P., Blum J. S., Kelner D. N., Marks M. S. Biosynthesis and processing of class II histocompatibility antigens. Crit Rev Immunol. 1987;7(1):31–53. [PubMed] [Google Scholar]
  2. Csiba A., Whitwell H. L., Moore M. Distribution of histocompatibility and leucocyte differentiation antigens in normal human colon and in benign and malignant colonic neoplasms. Br J Cancer. 1984 Nov;50(5):699–709. doi: 10.1038/bjc.1984.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Daar A. S., Fuggle S. V., Fabre J. W., Ting A., Morris P. J. The detailed distribution of HLA-A, B, C antigens in normal human organs. Transplantation. 1984 Sep;38(3):287–292. doi: 10.1097/00007890-198409000-00018. [DOI] [PubMed] [Google Scholar]
  4. Daar A. S., Fuggle S. V., Ting A., Fabre J. W. Anomolous expression of HLA-DR antigens on human colorectal cancer cells. J Immunol. 1982 Aug;129(2):447–449. [PubMed] [Google Scholar]
  5. Demant P. Histocompatibility and the genetics of tumour resistance. J Immunogenet. 1986 Apr-Jun;13(2-3):61–67. doi: 10.1111/j.1744-313x.1986.tb01085.x. [DOI] [PubMed] [Google Scholar]
  6. Doyle A., Martin W. J., Funa K., Gazdar A., Carney D., Martin S. E., Linnoila I., Cuttitta F., Mulshine J., Bunn P. Markedly decreased expression of class I histocompatibility antigens, protein, and mRNA in human small-cell lung cancer. J Exp Med. 1985 May 1;161(5):1135–1151. doi: 10.1084/jem.161.5.1135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Festenstein H. The biological consequences of altered MHC expression on tumours. Br Med Bull. 1987 Jan;43(1):217–227. doi: 10.1093/oxfordjournals.bmb.a072172. [DOI] [PubMed] [Google Scholar]
  8. Fleming K. A., McMichael A., Morton J. A., Woods J., McGee J. O. Distribution of HLA class 1 antigens in normal human tissue and in mammary cancer. J Clin Pathol. 1981 Jul;34(7):779–784. doi: 10.1136/jcp.34.7.779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fukusato T., Gerber M. A., Thung S. N., Ferrone S., Schaffner F. Expression of HLA class I antigens on hepatocytes in liver disease. Am J Pathol. 1986 May;123(2):264–270. [PMC free article] [PubMed] [Google Scholar]
  10. Giacoletto K. S., Sant A. J., Bono C., Gorka J., O'Sullivan D. M., Quaranta V., Schwartz B. D. The human invariant chain is the core protein of the human class II-associated proteoglycan. J Exp Med. 1986 Nov 1;164(5):1422–1439. doi: 10.1084/jem.164.5.1422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Goodenow R. S., Vogel J. M., Linsk R. L. Histocompatibility antigens on murine tumors. Science. 1985 Nov 15;230(4727):777–783. doi: 10.1126/science.2997918. [DOI] [PubMed] [Google Scholar]
  12. Jones P. P., Murphy D. B., Hewgill D., McDevitt H. O. Detection of a common polypeptide chain in I--A and I--E sub-region immunoprecipitates. Mol Immunol. 1979 Jan;16(1):51–60. doi: 10.1016/0161-5890(79)90027-0. [DOI] [PubMed] [Google Scholar]
  13. Kadin M. E. Ia-like (HLA-DR) antigens in the diagnosis of lymphoma and undifferentiated tumors. Arch Pathol Lab Med. 1980 Oct;104(10):503–508. [PubMed] [Google Scholar]
  14. Kew M. C., Geddes E. W. Hepatocellular carcinoma in rural southern African blacks. Medicine (Baltimore) 1982 Mar;61(2):98–108. doi: 10.1097/00005792-198203000-00004. [DOI] [PubMed] [Google Scholar]
  15. Kew M. C., Paterson A. C. Unusual clinical presentations of hepatocellular carcinoma. Trop Gastroenterol. 1985 Jan-Mar;6(1):10–22. [PubMed] [Google Scholar]
  16. Koch N., Harris A. W. Differential expression of the invariant chain in mouse tumor cells: relationship to B lymphoid development. J Immunol. 1984 Jan;132(1):12–15. [PubMed] [Google Scholar]
  17. Lafuse W. P., David C. S. Ia antigens: genes, molecules and function. Transplantation. 1984 Nov;38(5):443–453. doi: 10.1097/00007890-198411000-00001. [DOI] [PubMed] [Google Scholar]
  18. Lampert I. A., Kirkland S., Farrell S., Borysiewicz L. K. HLA-DR expression in a human colonic carcinoma cell line. J Pathol. 1985 Aug;146(4):337–344. doi: 10.1002/path.1711460407. [DOI] [PubMed] [Google Scholar]
  19. Lautenschlager I., Taskinen E., Inkinen K., Lehto V. P., Virtanen I., Häyry P. Distribution of the major histocompatibility complex antigens on different cellular components of human liver. Cell Immunol. 1984 Apr 15;85(1):191–200. doi: 10.1016/0008-8749(84)90289-2. [DOI] [PubMed] [Google Scholar]
  20. Long E. O. In search of a function for the invariant chain associated with Ia antigens. Surv Immunol Res. 1985;4(1):27–34. doi: 10.1007/BF02918583. [DOI] [PubMed] [Google Scholar]
  21. Momburg F., Degener T., Bacchus E., Moldenhauer G., Hämmerling G. J., Möller P. Loss of HLA-A,B,C and de novo expression of HLA-D in colorectal cancer. Int J Cancer. 1986 Feb 15;37(2):179–184. doi: 10.1002/ijc.2910370203. [DOI] [PubMed] [Google Scholar]
  22. Montano L., Miescher G. C., Goodall A. H., Wiedmann K. H., Janossy G., Thomas H. C. Hepatitis B virus and HLA antigen display in the liver during chronic hepatitis B virus infection. Hepatology. 1982 Sep-Oct;2(5):557–561. doi: 10.1002/hep.1840020508. [DOI] [PubMed] [Google Scholar]
  23. Moore M., Ghosh A. K. "Aberrant" MHC class II expression in epithelia. Lancet. 1987 Jan 17;1(8525):165–165. doi: 10.1016/s0140-6736(87)92004-6. [DOI] [PubMed] [Google Scholar]
  24. Möller P., Lämmler B., Herrmann B., Otto H. F., Moldenhauer G., Momburg F. The primary mediastinal clear cell lymphoma of B-cell type has variable defects in MHC antigen expression. Immunology. 1986 Nov;59(3):411–417. [PMC free article] [PubMed] [Google Scholar]
  25. Nagafuchi Y., Hobbs K. E., Thomas H. C., Scheuer P. J. Expression of beta-2-microglobulin on hepatocytes after liver transplantation. Lancet. 1985 Mar 9;1(8428):551–554. doi: 10.1016/s0140-6736(85)91209-7. [DOI] [PubMed] [Google Scholar]
  26. Nagafuchi Y., Scheuer P. J. Expression of beta 2-microglobulin on hepatocytes in acute and chronic type B hepatitis. Hepatology. 1986 Jan-Feb;6(1):20–23. doi: 10.1002/hep.1840060105. [DOI] [PubMed] [Google Scholar]
  27. Natali P. G., De Martino C., Quaranta V., Bigotti A., Pellegrino M. A., Ferrone S. Changes in Ia-like antigen expression on malignant human cells. Immunogenetics. 1981;12(3-4):409–413. doi: 10.1007/BF01561680. [DOI] [PubMed] [Google Scholar]
  28. Okuda K. Early recognition of hepatocellular carcinoma. Hepatology. 1986 Jul-Aug;6(4):729–738. doi: 10.1002/hep.1840060432. [DOI] [PubMed] [Google Scholar]
  29. Philipps C., McMillan M., Flood P. M., Murphy D. B., Forman J., Lancki D., Womack J. E., Goodenow R. S., Schreiber H. Identification of a unique tumor-specific antigen as a novel class I major histocompatibility molecule. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5140–5144. doi: 10.1073/pnas.82.15.5140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ponder B. A., Wilkinson M. M., Wood M., Westwood J. H. Immunohistochemical demonstration of H2 antigens in mouse tissue sections. J Histochem Cytochem. 1983 Jul;31(7):911–919. doi: 10.1177/31.7.6343482. [DOI] [PubMed] [Google Scholar]
  31. Quaranta V., Majdic O., Stingl G., Liszka K., Honigsmann H., Knapp W. A human Ia cytoplasmic determinant located on multiple forms of invariant chain (gamma, gamma 2, gamma 3). J Immunol. 1984 Apr;132(4):1900–1905. [PubMed] [Google Scholar]
  32. Ruiter D. J., Bröcker E. B., Ferrone S. Expression and susceptibility to modulation by interferons of HLA class I and II antigens on melanoma cells. Immunohistochemical analysis and clinical relevance. J Immunogenet. 1986 Apr-Jun;13(2-3):229–234. doi: 10.1111/j.1744-313x.1986.tb01105.x. [DOI] [PubMed] [Google Scholar]
  33. Saunders D. A., Beals T. F., Schultz J. S. Qualitative and quantitative evaluation of indirect immunofluorescent H-2 stain on tissue sections. Tissue Antigens. 1979 Aug;14(2):73–85. doi: 10.1111/j.1399-0039.1979.tb00826.x. [DOI] [PubMed] [Google Scholar]
  34. Schrier P. I., Bernards R., Vaessen R. T., Houweling A., van der Eb A. J. Expression of class I major histocompatibility antigens switched off by highly oncogenic adenovirus 12 in transformed rat cells. 1983 Oct 27-Nov 2Nature. 305(5937):771–775. doi: 10.1038/305771a0. [DOI] [PubMed] [Google Scholar]
  35. Sheu J. C., Sung J. L., Chen D. S., Yang P. M., Lai M. Y., Lee C. S., Hsu H. C., Chuang C. N., Yang P. C., Wang T. H. Growth rate of asymptomatic hepatocellular carcinoma and its clinical implications. Gastroenterology. 1985 Aug;89(2):259–266. doi: 10.1016/0016-5085(85)90324-5. [DOI] [PubMed] [Google Scholar]
  36. Sollid L. M., Gaudernack G., Markussen G., Kvale D., Brandtzaeg P., Thorsby E. Induction of various HLA class II molecules in a human colonic adenocarcinoma cell line. Scand J Immunol. 1987 Feb;25(2):175–180. doi: 10.1111/j.1365-3083.1987.tb01061.x. [DOI] [PubMed] [Google Scholar]
  37. Spiro R. C., Sairenji T., Humphreys R. E. Kinetics of Ii synthesis, processing, and turnover in n-butyrate-treated Burkitt's lymphoma cell lines which express or do not express class II antigens and in hairy leukemic cells. J Immunol. 1985 May;134(5):3539–3549. [PubMed] [Google Scholar]
  38. Strachan T. Molecular genetics and polymorphism of class I HLA antigens. Br Med Bull. 1987 Jan;43(1):1–14. doi: 10.1093/oxfordjournals.bmb.a072166. [DOI] [PubMed] [Google Scholar]
  39. Tanaka K., Isselbacher K. J., Khoury G., Jay G. Reversal of oncogenesis by the expression of a major histocompatibility complex class I gene. Science. 1985 Apr 5;228(4695):26–30. doi: 10.1126/science.3975631. [DOI] [PubMed] [Google Scholar]
  40. Wakasa K., Sakurai M., Okamura J., Kuroda C. Pathological study of small hepatocellular carcinoma: frequency of their invasion. Virchows Arch A Pathol Anat Histopathol. 1985;407(3):259–270. doi: 10.1007/BF00710651. [DOI] [PubMed] [Google Scholar]
  41. Whelan J. P., Chatten J., Lampson L. A. HLA class I and beta 2-microglobulin expression in frozen and formaldehyde-fixed paraffin sections of neuroblastoma tumors. Cancer Res. 1985 Nov;45(11 Pt 2):5976–5983. [PubMed] [Google Scholar]
  42. van den Ingh H. F., Ruiter D. J., Griffioen G., van Muijen G. N., Ferrone S. HLA antigens in colorectal tumours--low expression of HLA class I antigens in mucinous colorectal carcinomas. Br J Cancer. 1987 Feb;55(2):125–130. doi: 10.1038/bjc.1987.26. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. van den Oord J. J., de Vos R., Desmet V. J. In situ distribution of major histocompatibility complex products and viral antigens in chronic hepatitis B virus infection: evidence that HBc-containing hepatocytes may express HLA-DR antigens. Hepatology. 1986 Sep-Oct;6(5):981–989. doi: 10.1002/hep.1840060529. [DOI] [PubMed] [Google Scholar]

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