Clinical & Experimental Metastasis

, Volume 7, Issue 2, pp 213–226 | Cite as

Phenotypic expression of histocompatibility antigens in human primary tumours and metastases

  • Francisco Ruiz-Cabello
  • Miguel A. Lopez Nevot
  • Javier Gutierrez
  • Maria R. Oliva
  • Carlos Romero
  • Antonio Ferron
  • Francisco Esteban
  • Concepcion Huelin
  • Miguel A. Piris
  • Carmen Rivas
  • Federico Garrido


HLA class I and II expression was studied on 244 (177 primary and 67 metastatic) solid human tumours of different origin. Alkaline immunophosphatase (APAAP) and immunoperoxidase were used on cryostatic sections to stain MHC antigens. Monomorphic MoAbs were used against class I heavy chain, β2-microglobulin, DR, DQ and DP molecules.

Class I expression was homogeneous on colon, melanoma and epidermoidal primitive tumours. Loss of HLA class I antigens was more frequent on basal cell carcinomas and sarcomas and was related to tumour differentiation on larynx carcinoma. Class I expression was heterogeneous on breast, larynx and stomach primitive neoplasias. Class I negative tumours were more frequent on metastatic than on primitive melanomas. Divergence of class I between primary tumours and autologous metastases was observed on melanomas, larynx and colorectal carcinomas.

Class II expression was heterogeneous on all tumours and in a large number of cases was associated with high intensity of leukocytic infiltrate. HLA-DR expression was higher than HLA-DP and HLA-DQ (DR>DP>DQ) and was related to tumour progression. Four human tumour cell lines were modulated with recombinant interferon-γ for HLA class I and II antigens. Different HLA profiles were obtained: increased class I and II expression, increased class II or a low response.

Finally, class I genes from 22 tumours were compared with autologous normal cells by Southern blot analysis: 12 tumours were class I positive and 10 negative. No clear differences in RFLP were observed that could be associated with class I rearrangement. The results are discussed in relation to the role that histocompatibility antigens may play in tumour progression and invasiveness.


Melanoma Southern Blot Analysis Basal Cell Carcinoma Cryostatic Section Human Tumour Cell Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    Albino, A. P., Houghton, A. N., Eisenger, M., Lee, J. S., Kantor, R. R. S., Oliff, A., andOld, L. J., 1986, Class II histocompatibility antigen expression in human melanocytes transformed by Harvey murine sarcoma virus (Ha-MSV) and Kirsten MSV retroviruses.Journal of Experimental Medicine,164, 1710–1722.PubMedGoogle Scholar
  2. [2]
    Altevogt, P., Leidig, S., andOestreicher, B. H., 1984, Resistence of metastatic tumour variants to tumour specific cytotoxic T lymphocytes not due to defects in expression of restricting major histocompatibility complex molecules in murine cells.Cancer Research,44, 5305–5310.PubMedGoogle Scholar
  3. [3]
    Barnstable, C. J., Bodmer, W. F., Brown, G., Glafre, G., Milstein, C., Williams, A. F., andZiegler, A., 1978, A production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens. New tools for genetic analysis.Cell,14, 9–20.PubMedGoogle Scholar
  4. [4]
    Bashman, T. Y., andMerigan, T., 1983, Recombinant interferon-γ increase HLA-DR synthesis and expression.Journal of Immunology,130, 1492–1494.Google Scholar
  5. [5]
    Bergman, W., Willemze, R., De Graaf-Reitsma, C. B., andRuiter, D. J., 1985, Analysis of major histocompatibility antigens and mononuclear cell infiltrate in halo nevi,Journal of Investigative Dermatology,85, 25–29.PubMedGoogle Scholar
  6. [6]
    Bernards, R., Schrier, P. I., Houweling, A., Bos, F. L., van der Eb, A. J., Zijlstra, M., andMelief, C. J. M., 1983, Tumorigenicity of cells transformed by adenovirus type 12 by evasion of T-cell immunity.Nature (London),305, 776–779.Google Scholar
  7. [7]
    Blin, N., andStadford, D. W., 1976, Isolation of high-molecular-weight DNA.Nucleic Acids Research,3, 2303–2307.PubMedGoogle Scholar
  8. [8]
    Bröcker, E. B., Suter, L., Bruggen, J., Ruiter, D. J., Macher, E., andSorg, S., 1985, Phenotypic dynamics of tumor progression in human malignant melanoma.International Journal of Cancer,36, 29–35.Google Scholar
  9. [9]
    Cabrera, T., Ruiz-Cabello, F., Lopez Nevot, M. A., de la Higuera, B., Sanchez, M., andGarrido, F., 1986, Characterization of monoclonal antibodies directed against HLA class II antigens.Hybridoma,5, 191–197.PubMedGoogle Scholar
  10. [10]
    Carrel, S., Schmidt, A., andGiuffré, L., 1985, Recombinant interferon-γ can induce the expression of HLA-DR and DC on DR-negative melanomas cells and enhance the expression of HLA-ABC and tumor-associated antigens.European Journal of Immunology,15, 118–123.PubMedGoogle Scholar
  11. [11]
    Daar, A. S., Fuggle, S. V., Fabre, J. W., Ting, A., andMorris. P. J., 1984, The detailed distribution of HLA ABC antigens in normal human organs.Transplantation,38, 287–292.PubMedGoogle Scholar
  12. [12]
    De Baetselier, P., Katzav, S., Gorelik, E., Feldman, M., andSegal, S., 1980, Differential expression of H-2 gene products in tumor cells is associated with their metastogenic properties.Nature (London),288, 179.Google Scholar
  13. [13]
    Doyle, A., Martin, W. J., Funa, K., Gazdar, A., Carney, D., Martin, S. E., Linnoila, I., Cuttitta, F., Mulshine, J., Bunn, P., andMinna, J., 1985, Markedly decreased expression of class I histocompatibility antigens, protein and mRNA in human small cell lung cancer.Journal of Experimental Medicine,161, 1135–1151.PubMedGoogle Scholar
  14. [14]
    Eckels, D. D., Lake, P., Lamb, J. R., Johnson, A. H., Shaw, S., Woody, J. N., andHartzman, R. J., 1983, SB restricted presentation of influenza and herpes simplex virus antigen to human T lymphocyte clones.Nature (London),301, 716–718.Google Scholar
  15. [15]
    Festenstein, H., andGarrido, F., 1986, MHC antigens and malignancy.Nature (London),322, 502–503.Google Scholar
  16. [16]
    Festenstein, H., Garrido, F., Matossian-Rogers, A., Schirrmacher, V., Schmidt, W., De Giorgi, L., Biasi, G., andJaraquemada, D., 1977, The major histocompatibility system, tumours and viruses.HLA system. New Aspects, Edited by G. B. Ferrara (Amsterdam: Elsevier/North-Holland Biomedical Press), pp. 53–67.Google Scholar
  17. [17]
    Garrido, A., Perez, M., Delgado, C., Garrido, M. L., Rojano, J., Algarra, I., andGarrido, F., 1986, The influence of class I H-2 gene expression on local tumor growth. Description of a model obtained from clones derived from a solid BALB/c tumor.Experimental Clinical Immunogenetics,3, 98–110.Google Scholar
  18. [18]
    Garrido, F., 1988, The biological implications of the abnormal expression of histocompatibility antigens on murine and human tumors.Bar Harbor, Maine, U.S.A., June 1987, edited by C. S. David (New York: Plenum Press), NATO ASI Series, Vol. 144, pp. 623–639.Google Scholar
  19. [19]
    Goodenow, R. S., Vogel, J.M., andLinsk, R. L., 1985, Histocompatibility antigens on murine tumors.Science,230, 777–783.PubMedGoogle Scholar
  20. [20]
    Gutierrez, J., Lopez Nevot, M.A., Cabrera, T., Oliva, R., Esquivias, J., RuizCabello, F., andGarrido, F., 1987. Class I and II HLA antigen distribution in normal mucosa, adenoma and colon carcinoma: relation with malignancy and invasiveness.Experimental Clinical Immunogenetics,4, 144–152.Google Scholar
  21. [21]
    Hui, K., Grosveld, F., andFestenstein, H., 1984, Rejection of transplantable AKR leukaemia cells following MHC-DNA mediated cell transformation.Nature (London),310, 750–752.Google Scholar
  22. [22]
    Jass, J. R., Atkin, W. S., Cuzick, J., Bussey, H. J. R., Morson, B. C., Northover, J. M. A., andTood, I. P., 1986, The grading of colorectal carcinomas: historical perspectives and a multivariate analyses of 447 cases.Histopathology,10, 437–459.Google Scholar
  23. [23]
    Karre, K., Ljunggren, H. G., Pionteck, G., andKiessling, R., 1986, Selective rejection of H2 deficient lymphoma variants suggest alternative defence strategy.Nature (London),319, 675–678.Google Scholar
  24. [24]
    Lopez Nevot, M. A., Cabrera, T., De la Higuera, B., Ruiz-Cabello, F., andGarrido, F., 1986, Production and characterization of monoclonal antibodies against leukemic cells.Inmunologia,5, 51–59.Google Scholar
  25. [25]
    Lopez Nevot, M. A., Garcia, E., Pareja, E., Bonal, F. J., Martin, J., Ruiz-Cabello, F., andGarrido, F., 1986, Differential expression of HLA antigens in primary and metastatic melanomas.Journal of Immunogenetics,16, 219–227.Google Scholar
  26. [26]
    Lopez Nevot, M. A.,Esteban, F.,Ferron, A.,Gutierrez, J.,Oliva, R.,Romero, C.,Huelin, C.,Ruiz-Cabello, F., andGarrido, F., 1988. HLA class I gene expression on human primary tumors and autologous metastases: Demonstration of selective losses of HLA antigens on colorectal, gastric and laryngeal carcinomas.British Journal of Cancer (in press).Google Scholar
  27. [27]
    Ljunggren, H. G., andKarre, K., 1986, Experimental strategies and interpretations in the analysis of changes in MHC gene expression during tumour progression.Journal of Immunogenetics,13, 141–151.PubMedGoogle Scholar
  28. [28]
    Perez, M., Cabrera, T., Lopez Nevot, M. A., Gomez, M., Peran, F., Ruiz-Cabello, F., andGarrido, F., 1986, Heterogeneity of the expression of class I and II antigens in human breast carcinomas.Journal of Immunogenetics,13, 247–253.PubMedGoogle Scholar
  29. [29]
    Ploegh, H. L., Orr, H. T., andStrominger, J. L., 1981, Major histocompatibility antigens: the human (HLA A-B-C) and murine (H2K, H2D) class I molecules.Cell,24, 287–299.PubMedGoogle Scholar
  30. [30]
    Rogers, M. J., Gooding, L. R., Margulies, D. H., andEvans, G. A., 1983, Analysis of a defect in the H2 genes of SV40 transformed C3H fibroblast that do not express H-2Kk.Journal of Immunology,130, 2418–2422.Google Scholar
  31. [31]
    Ruiter, D. J., Bröcker, E. B., andFerrone, S., 1986, Expression and susceptibility to modulation by interferons of HLA class I and II antigens on melanoma cells. Immunohistochemical analysis and clinical relevance.Journal of Immunogenetics,13, 229–234.PubMedGoogle Scholar
  32. [32]
    Shackelford, D. A., Kaufman, J. F., Korman, A. J., andStrominger, S. L., 1982, HLA-DR antigens: structure, separation of subpopulations, gene cloning and function.Immunology Reviews,66, 133–151.Google Scholar
  33. [33]
    Sood, A. K., Pereira, D., Weissman, S. M., 1981, Isolation and partial nucleotide sequence of a cDNA clone for human histocompatibility antigen HLA-B by use of an oligodeoxynucleotide primer.Proceedings of the National Academy of Sciences, U.S.A.,78, 616–620.Google Scholar
  34. [34]
    Southern, E., 1975, Detection of specific sequences among DNA fragments separated by gel electrophoresis.Journal of Molecular Biology,98, 503–518.PubMedGoogle Scholar
  35. [35]
    Trowsdale, J., Travers, P., Bodmer, F., andPatillo, R. A., 1980, Expression of HLA ABC., and β2-microglobulin antigens in human choriocarcinoma cell lines.Journal of Experimental Medicine,152, 11–17 (Suppl.).Google Scholar
  36. [36]
    Ucer, U., Bartsch, H., Scheurich, P., andPfizenmaier, K., 1985, Biological effects of cell membrane receptors forγ-IFN in relation to growth inhibition and induction of HLA-DR expression.International Journal of Cancer,36, 103–108.Google Scholar
  37. [37]
    Watson, A. J., DeMars, R., Trowbridge, I. S., andBach, F. H., 1983, Detection of a novel human HLA antigen.Nature (London),304, 358–361.Google Scholar
  38. [38]
    Ziegler, A., Uchaska-Ziegler, B., Rosenfelder, G., Braun, D. G., andWernet, P., 1981, Heterogeneity of established human hematopoietic cell lines.Leukaemia markers.Proceedings of the Leukaemia Marker Conference, Vienna, February, 1981 (New York: Academic Press), pp. 137–159.Google Scholar
  39. [39]
    Zinkernagel, R. M., andDoherty, P. C., 1979, MHC restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determing T cell restriction specificity function and responsiveness.Advances in Immunology,27, 51–77.PubMedGoogle Scholar

Copyright information

© Taylor & Francis Ltd 1989

Authors and Affiliations

  • Francisco Ruiz-Cabello
  • Miguel A. Lopez Nevot
  • Javier Gutierrez
    • 1
  • Maria R. Oliva
  • Carlos Romero
  • Antonio Ferron
    • 2
  • Francisco Esteban
    • 3
  • Concepcion Huelin
  • Miguel A. Piris
    • 4
  • Carmen Rivas
    • 4
  • Federico Garrido
  1. 1.Servicio de Analisis ClinicosHospital Virgen de las NievesGranadaSpain
  2. 2.Departamento de CirugíaHospital Virgen de las NievesGranadaSpain
  3. 3.Servicio de OtorrinolaringologíaHospital Virgen de las NievesGranadaSpain
  4. 4.Servicio de Anatomia PatologicaFundación Jimenez DíazMadridSpain

Personalised recommendations