Abstract
The expression of HLA class I antigens was studied in 99 primary tumour (colorectal, gastric and laryngeal carcinomas) and 57 autologous metastases using immunohistological techniques and monoclonal antibodies against class I monomorphic determinants, HLA-B isotypic determinants and HLA polymorphic determinants. Fourteen per cent of colorectal, 9.6% of gastric and 20% of laryngeal carcinomas completely lacked class I molecules. Selective losses of HLA-B antigens were also detected in 8.8, 3.4 and 5.8% of these tumours respectively. Taking into account complete and selective loss of HLA-B the average alteration in the class I molecules expression totalled 21%. The comparison of class I expression between primary tumours and autologous metastases showed differences in 24% of the patients. These differences consisted mainly in a decrease of class I expression by metastases. Nevertheless, four types of divergence were detected in laryngeal carcinomas, namely: +/-, +/+, -/+, -/-. In addition, a clear correlation between degree of differentiation and class I expression was observed in laryngeal tumours. Finally, when class I gene RFLPs were compared with DNA from 15 tumours and autologous normal mucosa or peripheral lymphocytes, no differences were detected between these samples.
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- Albino A. P., Lloyd K. O., Houghton A. N., Oettgen H. F., Old L. J. Heterogeneity in surface antigen and glycoprotein expression of cell lines derived from different melanoma metastases of the same patient. Implications for the study of tumor antigens. J Exp Med. 1981 Dec 1;154(6):1764–1778. doi: 10.1084/jem.154.6.1764. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Angelini G., Fossati G., Radice P., Longo A., Piccioli P., Pierotti M. A., Ferrara G. B., Parmiani G. Loss of polymorphic restriction fragments of class I and class II MHC genes in a malignant melanoma. J Immunogenet. 1986 Apr-Jun;13(2-3):241–246. doi: 10.1111/j.1744-313x.1986.tb01107.x. [DOI] [PubMed] [Google Scholar]
- Bar-Eli M., Battifora H., Cline M. J. Alterations of class I HLA genes in human colon cancers. Hum Genet. 1988 Jan;78(1):86–89. doi: 10.1007/BF00291242. [DOI] [PubMed] [Google Scholar]
- Blin N., Stafford D. W. A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res. 1976 Sep;3(9):2303–2308. doi: 10.1093/nar/3.9.2303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bonal F. J., Pareja E., Martin J., Romero C., Garrido F. Repression of class I H-2K, H-2D antigens on GR9 methylcholanthrene-induced tumour cell clones is related to the level of DNA methylation. J Immunogenet. 1986 Apr-Jun;13(2-3):179–186. doi: 10.1111/j.1744-313x.1986.tb01099.x. [DOI] [PubMed] [Google Scholar]
- Burrone O. R., Kefford R. F., Gilmore D., Milstein C. Stimulation of HLA-A,B,C by IFN-alpha. The derivation of Molt 4 variants and the differential expression of HLA-A,B,C subsets. EMBO J. 1985 Nov;4(11):2855–2860. doi: 10.1002/j.1460-2075.1985.tb04014.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
- Cullen S. E., David C. S., Shreffler D. C., Nathenson S. G. Membrane molecules determined by the H-2 associated immune response region: isolation and some properties. Proc Natl Acad Sci U S A. 1974 Mar;71(3):648–652. doi: 10.1073/pnas.71.3.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Dausset J. The major histocompatibility complex in man. Science. 1981 Sep 25;213(4515):1469–1474. doi: 10.1126/science.6792704. [DOI] [PubMed] [Google Scholar]
- 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]
- Eisenbach L., Segal S., Feldman M. MHC imbalance and metastatic spread in Lewis lung carcinoma clones. Int J Cancer. 1983 Jul 15;32(1):113–120. doi: 10.1002/ijc.2910320118. [DOI] [PubMed] [Google Scholar]
- Engleman E. G., Charron D. J., Benike C. J., Stewart G. J. Ia antigen on peripheral blood mononuclear leukocytes in man. I. Expression, biosynthesis, and function of HLA-DR antigen non-T cells. J Exp Med. 1980 Aug 1;152(2 Pt 2):99s–113s. [PubMed] [Google Scholar]
- Festenstein H., Garrido F. MHC antigens and malignancy. Nature. 1986 Aug 7;322(6079):502–503. doi: 10.1038/322502a0. [DOI] [PubMed] [Google Scholar]
- Festenstein H., Schmidt W. Variation in MHC antigenic profiles of tumor cells and its biological effects. Immunol Rev. 1981;60:85–127. doi: 10.1111/j.1600-065x.1981.tb00363.x. [DOI] [PubMed] [Google Scholar]
- 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]
- Garrido F., Festenstein H., Schirrmacher V. Further evidence for depression of H-2 and Ia-like specificities of foreign haplotypes in mouse tumour cell lines. Nature. 1976 Jun 24;261(5562):705–707. doi: 10.1038/261705a0. [DOI] [PubMed] [Google Scholar]
- Garrido F., Perez M., Torres M. D. Absence of four H-2d antigenic specificites in an H-2d sarcoma. J Immunogenet. 1979 Apr;6(2):83–86. doi: 10.1111/j.1744-313x.1979.tb00333.x. [DOI] [PubMed] [Google Scholar]
- Garrido F., Schirrmacher V., Festenstein H. H-2-like specificities of foreign haplotypes appearing on a mouse sarcoma after vaccinia virus infection. Nature. 1976 Jan 22;259(5540):228–230. doi: 10.1038/259228a0. [DOI] [PubMed] [Google Scholar]
- Gmür R., Solter D., Knowles B. B. Independent regulation of H-2K and H-2D gene expression in murine teratocarcinoma somatic cell hybrids. J Exp Med. 1980 Jun 1;151(6):1349–1359. doi: 10.1084/jem.151.6.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gutierrez J., López-Nevot M. A., Cabrera T., Oliva R., Esquivias J., Ruiz-Cabello F., Garrido F. Class I and II HLA antigen distribution in normal mucosa, adenoma and colon carcinoma: relation with malignancy and invasiveness. Exp Clin Immunogenet. 1987;4(3):144–152. [PubMed] [Google Scholar]
- Kärre K., Ljunggren H. G., Piontek G., Kiessling R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature. 1986 Feb 20;319(6055):675–678. doi: 10.1038/319675a0. [DOI] [PubMed] [Google Scholar]
- Lampson L. A., Fisher C. A., Whelan J. P. Striking paucity of HLA-A, B, C and beta 2-microglobulin on human neuroblastoma cell lines. J Immunol. 1983 May;130(5):2471–2478. [PubMed] [Google Scholar]
- Ljunggren H. G., Kärre K. Experimental strategies and interpretations in the analysis of changes in MHC gene expression during tumour progression. Opposing influences of T cell and natural killer mediated resistance? J Immunogenet. 1986 Apr-Jun;13(2-3):141–151. doi: 10.1111/j.1744-313x.1986.tb01095.x. [DOI] [PubMed] [Google Scholar]
- Lopez Nevot M. A., Garcia E., Pareja E., Bonal F. J., Martin J., Ruiz-Cabello F., Serrano S., Garrido F. Differential expression of HLA class I and II antigens in primary and metastatic melanomas. J Immunogenet. 1986 Apr-Jun;13(2-3):219–227. doi: 10.1111/j.1744-313x.1986.tb01104.x. [DOI] [PubMed] [Google Scholar]
- Meruelo D., Kornreich R., Rossomando A., Pampeno C., Boral A., Silver J. L., Buxbaum J., Weiss E. H., Devlin J. J., Mellor A. L. Lack of class I H-2 antigens in cells transformed by radiation leukemia virus is associated with methylation and rearrangement of H-2 DNA. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4504–4508. doi: 10.1073/pnas.83.12.4504. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Möller P., Herrmann B., Moldenhauer G., Momburg F. Defective expression of MHC class I antigens is frequent in B-cell lymphomas of high-grade malignancy. Int J Cancer. 1987 Jul 15;40(1):32–39. doi: 10.1002/ijc.2910400107. [DOI] [PubMed] [Google Scholar]
- Natali P. G., Giacomini P., Bigotti A., Imai K., Nicotra M. R., Ng A. K., Ferrone S. Heterogeneity in the expression of HLA and tumor-associated antigens by surgically removed and cultured breast carcinoma cells. Cancer Res. 1983 Feb;43(2):660–668. [PubMed] [Google Scholar]
- Orgad S., Yang S. Y., Gazit E., Relias V., Zaizov R., Lyson S., Yunis E. J. Expression of extra class I major histocompatibility antigens on T-cell acute lymphoblastic leukemia (ALL) lymphoblasts. Hum Immunol. 1985 Mar;12(3):133–141. doi: 10.1016/0198-8859(85)90331-3. [DOI] [PubMed] [Google Scholar]
- Philipps C., Stauss H. J., Wortzel R. D., Schreiber H. A novel MHC class I molecule as a tumour-specific antigen. Correlation between the antibody-defined and the CTL-defined target structure. J Immunogenet. 1986 Apr-Jun;13(2-3):93–99. doi: 10.1111/j.1744-313x.1986.tb01089.x. [DOI] [PubMed] [Google Scholar]
- Ploegh H. L., Orr H. T., Strominger J. L. Major histocompatibility antigens: the human (HLA-A, -B, -C) and murine (H-2K, H-2D) class I molecules. Cell. 1981 May;24(2):287–299. doi: 10.1016/0092-8674(81)90318-4. [DOI] [PubMed] [Google Scholar]
- Pérez M., Cabrera T., Lopez Nevot M. A., Gomez M., Peran F., Ruiz-Cabello F., Garrido F. Heterogeneity of the expression of class I and II HLA antigens in human breast carcinoma. J Immunogenet. 1986 Apr-Jun;13(2-3):247–253. doi: 10.1111/j.1744-313x.1986.tb01108.x. [DOI] [PubMed] [Google Scholar]
- Rogers M. J., Gooding L. R., Margulies D. H., Evans G. A. Analysis of a defect in the H-2 genes of SV40 transformed C3H fibroblasts that do not express H-2Kk. J Immunol. 1983 May;130(5):2418–2422. [PubMed] [Google Scholar]
- Schirrmacher V., Robinson P., Altevogt P., Radbruch A., Garrido F., Koszinowski U., Krog H. H., Lundin L. Clonal analysis of H-2 antigen expression by variants of a chemically induced murine tumor. Transplant Proc. 1981 Dec;13(4):1819–1823. [PubMed] [Google Scholar]
- Smith M. E., Bodmer W. F., Bodmer J. G. Selective loss of HLA-A,B,C locus products in colorectal adenocarcinoma. Lancet. 1988 Apr 9;1(8589):823–824. doi: 10.1016/s0140-6736(88)91682-0. [DOI] [PubMed] [Google Scholar]
- Sood A. K., Pereira D., Weissman S. M. Isolation and partial nucleotide sequence of a cDNA clone for human histocompatibility antigen HLA-B by use of an oligodeoxynucleotide primer. Proc Natl Acad Sci U S A. 1981 Jan;78(1):616–620. doi: 10.1073/pnas.78.1.616. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- TERASAKI P. I., MCCLELLAND J. D. MICRODROPLET ASSAY OF HUMAN SERUM CYTOTOXINS. Nature. 1964 Dec 5;204:998–1000. doi: 10.1038/204998b0. [DOI] [PubMed] [Google Scholar]
- Zinkernagel R. M., Doherty P. C. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature. 1974 Apr 19;248(5450):701–702. doi: 10.1038/248701a0. [DOI] [PubMed] [Google Scholar]


