Abstract
MHC class I antigens are intimately involved in intercellular communication, and recognition by cytotoxic T cells. Thus tumour cells that fail to express them may be at a growth or metastatic advantage. A series of ten colorectal and ten breast carcinomas, and their respective lymph node metastases, were examined immunohistologically using monoclonal antibodies (mAb) against both monomorphic and A2 polymorphic determinants, and beta-2-microglobulin (beta 2m). Four colon polypoid adenomas stained positively throughout, but 6/10 primary tumours had partial or complete loss of expression of monomorphic determinants using mAb W6/32: two node and the liver metastasis showed less, four more expression. Similar results were seen for beta 2m. HLA-A2 expression was absent or reduced in 4/4 colon tumours and all their metastases. Among the breast tumours, W6/32 staining was absent or reduced in 2/10, and node deposits showed two with less reactivity than their primary. Beta 2m staining was reduced or absent in 8/10 primaries and all the node metastases; in every case in which beta 2m was detected in the primary tumour their corresponding lymph node metastasis showed a decreased expression. HLA-A2 expression was absent or reduced in 3/4 primary breast carcinomas, and all their metastases. These results show that individual human colon and breast carcinomas often have a reduced HLA class I antigen expression, which apparently confers a metastatic advantage.
Full text
PDF



Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arce-Gomez B., Jones E. A., Barnstable C. J., Solomon E., Bodmer W. F. The genetic control of HLA-A and B antigens in somatic cell hybrids: requirement for beta2 microglobulin. Tissue Antigens. 1978 Feb;11(2):96–112. doi: 10.1111/j.1399-0039.1978.tb01233.x. [DOI] [PubMed] [Google Scholar]
- Benacerraf B. Role of MHC gene products in immune regulation. Science. 1981 Jun 12;212(4500):1229–1238. doi: 10.1126/science.6165083. [DOI] [PubMed] [Google Scholar]
- Brodsky F. M., Bodmer W. F., Parham P. Characterization of a monoclonal anti-beta 2-microglobulin antibody and its use in the genetic and biochemical analysis of major histocompatibility antigens. Eur J Immunol. 1979 Jul;9(7):536–545. doi: 10.1002/eji.1830090709. [DOI] [PubMed] [Google Scholar]
- Brodsky F. M., Parham P., Barnstable C. J., Crumpton M. J., Bodmer W. F. Monoclonal antibodies for analysis of the HLA system. Immunol Rev. 1979;47:3–61. doi: 10.1111/j.1600-065x.1979.tb00288.x. [DOI] [PubMed] [Google Scholar]
- Bröcker E. B., Suter L., Sorg C. HLA-DR antigen expression in primary melanomas of the skin. J Invest Dermatol. 1984 Mar;82(3):244–247. doi: 10.1111/1523-1747.ep12260181. [DOI] [PubMed] [Google Scholar]
- Eisenbach L., Hollander N., Greenfeld L., Yakor H., Segal S., Feldman M. The differential expression of H-2K versus H-2D antigens, distinguishing high-metastatic from low-metastatic clones, is correlated with the immunogenic properties of the tumor cells. Int J Cancer. 1984 Oct 15;34(4):567–573. doi: 10.1002/ijc.2910340421. [DOI] [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]
- Esteban F., Concha A., Huelin C., Pérez-Ayala M., Pedrinaci S., Ruiz-Cabello F., Garrido F. Histocompatibility antigens in primary and metastatic squamous cell carcinoma of the larynx. Int J Cancer. 1989 Mar 15;43(3):436–442. doi: 10.1002/ijc.2910430316. [DOI] [PubMed] [Google Scholar]
- Haliotis T., Carlow D. A., Elliott B. E. Nonimmunological aspects of MHC function in the regulation of cell proliferation and the malignant phenotype. Cancer Cells. 1990 Mar;2(3):86–90. [PubMed] [Google Scholar]
- Haybittle J. L., Blamey R. W., Elston C. W., Johnson J., Doyle P. J., Campbell F. C., Nicholson R. I., Griffiths K. A prognostic index in primary breast cancer. Br J Cancer. 1982 Mar;45(3):361–366. doi: 10.1038/bjc.1982.62. [DOI] [PMC free article] [PubMed] [Google Scholar]
- López-Nevot M. A., Esteban F., Ferrón A., Gutiérrez J., Oliva M. R., Romero C., Huelin C., Ruiz-Cabello F., Garrido F. HLA class I gene expression on human primary tumours and autologous metastases: demonstration of selective losses of HLA antigens on colorectal, gastric and laryngeal carcinomas. Br J Cancer. 1989 Feb;59(2):221–226. doi: 10.1038/bjc.1989.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Masucci M. G., Torsteindottir S., Colombani J., Brautbar C., Klein E., Klein G. Down-regulation of class I HLA antigens and of the Epstein-Barr virus-encoded latent membrane protein in Burkitt lymphoma lines. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4567–4571. doi: 10.1073/pnas.84.13.4567. [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]
- Momburg F., Koch S. Selective loss of beta 2-microglobulin mRNA in human colon carcinoma. J Exp Med. 1989 Jan 1;169(1):309–314. doi: 10.1084/jem.169.1.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Müller H., Stutte H. J. MHC-Antigenexpression, Proliferationsaktivität und nodaler Metastasierungsstatus in 184 invasiven duktalen Mammakarzinomen. Verh Dtsch Ges Pathol. 1988;72:260–264. [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]
- 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]
- Rees R. C., Buckle A. M., Gelsthorpe K., James V., Potter C. W., Rogers K., Jacob G. Loss of polymorphic A and B locus HLA antigens in colon carcinoma. Br J Cancer. 1988 Apr;57(4):374–377. doi: 10.1038/bjc.1988.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ruiz-Cabello F., Lopez Nevot M. A., Gutierrez J., Oliva M. R., Romero C., Ferron A., Esteban F., Huelin C., Piris M. A., Rivas C. Phenotypic expression of histocompatibility antigens in human primary tumours and metastases. Clin Exp Metastasis. 1989 Mar-Apr;7(2):213–226. doi: 10.1007/BF01787025. [DOI] [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]
- Smith M. E., Marsh S. G., Bodmer J. G., Gelsthorpe K., Bodmer W. F. Loss of HLA-A,B,C allele products and lymphocyte function-associated antigen 3 in colorectal neoplasia. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5557–5561. doi: 10.1073/pnas.86.14.5557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]



