Abstract
Expression of HLA antigens and beta 2-microglobulin was studied by immunoperoxidase staining of frozen sections of 9 mucinous and 10 nonmucinous colorectal adenocarcinomas, 1 cloacogenic carcinoma, 12 colorectal adenomas and 4 samples of normal colorectal mucosa using monoclonal antibodies (MAbs). Staining results were related to histopathological features. HLA Class I antigens were strongly expressed in morphologically normal colorectal epithelium, in all adenomas tested and in all non-mucinous carcinomas. In contrast, expression of HLA class I antigens by the majority of tumour cells was present in only 2 of the 9 mucinous carcinomas, whereas 2 of these mucinous carcinomas were completely negative. In the mucinous carcinomas a striking scarcity of mononuclear inflammatory infiltrate, especially around the mucus accumulations, was observed. HLA class II antigen expression was not detected in normal epithelium and was only focally present in 1 of the 12 adenomas. In 6 out of the 20 carcinomas tested between 20% and 90% of the tumour cells were stained by MAbs against HLA class II antigens. Apart from the low expression of HLA class I antigens in mucinous carcinomas no relationship was found between expression of HLA antigens and histological features of the tumours. The relative poor prognosis of mucinous colorectal carcinoma as reported in the literature may be associated with low expression of HLA class I antigens and scant mononuclear inflammatory infiltrate, which may be a reflection of a weak immune response to the tumour cells.
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- Almagro U. A. Primary signet-ring carcinoma of the colon. Cancer. 1983 Oct 15;52(8):1453–1457. doi: 10.1002/1097-0142(19831015)52:8<1453::aid-cncr2820520819>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
- Barlogie B., Drewinko B., Schumann J., Göhde W., Dosik G., Latreille J., Johnston D. A., Freireich E. J. Cellular DNA content as a marker of neoplasia in man. Am J Med. 1980 Aug;69(2):195–203. doi: 10.1016/0002-9343(80)90379-4. [DOI] [PubMed] [Google Scholar]
- Bernards R., Schrier P. I., Houweling A., Bos J. L., van der Eb A. J., Zijlstra M., Melief C. J. Tumorigenicity of cells transformed by adenovirus type 12 by evasion of T-cell immunity. 1983 Oct 27-Nov 2Nature. 305(5937):776–779. doi: 10.1038/305776a0. [DOI] [PubMed] [Google Scholar]
- Bhan A. K., DesMarais C. L. Immunohistologic characterization of major histocompatibility antigens and inflammatory cellular infiltrate in human breast cancer. J Natl Cancer Inst. 1983 Sep;71(3):507–516. [PubMed] [Google Scholar]
- Black P. H. Shedding from normal and cancer-cell surfaces. N Engl J Med. 1980 Dec 11;303(24):1415–1416. doi: 10.1056/NEJM198012113032411. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- De Baetselier P., Katzav S., Gorelik E., Feldman M., Segal S. Differential expression of H-2 gene products in tumour cells in associated with their metastatogenic properties. Nature. 1980 Nov 13;288(5787):179–181. doi: 10.1038/288179a0. [DOI] [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
- 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]
- Howe A. J., Seeger R. C., Molinaro G. A., Ferrone S. Analysis of human tumor cells for Ia-like antigens with monoclonal antibodies. J Natl Cancer Inst. 1981 May;66(5):827–829. [PubMed] [Google Scholar]
- Kabawat S. E., Bast R. C., Jr, Welch W. R., Knapp R. C., Bhan A. K. Expression of major histocompatibility antigens and nature of inflammatory cellular infiltrate in ovarian neoplasms. Int J Cancer. 1983 Nov 15;32(5):547–554. doi: 10.1002/ijc.2910320505. [DOI] [PubMed] [Google Scholar]
- Krangel M. S., Orr H. T., Strominger J. L. Assembly and maturation of HLA-A and HLA-B antigens in vivo. Cell. 1979 Dec;18(4):979–991. doi: 10.1016/0092-8674(79)90210-1. [DOI] [PubMed] [Google Scholar]
- Mauduit G., Turbitt M., MacKie R. M. Dissociation of HLA heavy chain and light chain (beta 2 microglobulin) expression on the cell surface of cutaneous malignancies. Br J Dermatol. 1983 Oct;109(4):377–381. doi: 10.1111/j.1365-2133.1983.tb04611.x. [DOI] [PubMed] [Google Scholar]
- McMichael A. J. HLA restriction of human cytotoxic T cells. Springer Semin Immunopathol. 1980 May;3(1):3–22. doi: 10.1007/BF00199923. [DOI] [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]
- Nacopoulou L., Azaris P., Papacharalampous N., Davaris P. Prognostic significance of histologic host response in cancer of the large bowel. Cancer. 1981 Mar 1;47(5):930–936. doi: 10.1002/1097-0142(19810301)47:5<930::aid-cncr2820470519>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
- Natali P. G., Bigotti A., Nicotra M. R., Viora M., Manfredi D., Ferrone S. Distribution of human Class I (HLA-A,B,C) histocompatibility antigens in normal and malignant tissues of nonlymphoid origin. Cancer Res. 1984 Oct;44(10):4679–4687. [PubMed] [Google Scholar]
- 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]
- 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]
- Natali P. G., Viora M., Nicotra M. R., Giacomini P., Bigotti A., Ferrone S. Antigenic heterogeneity of skin tumors of nonmelanocyte origin: analysis with monoclonal antibodies to tumor-associated antigens and to histocompatibility antigens. J Natl Cancer Inst. 1983 Sep;71(3):439–447. [PubMed] [Google Scholar]
- Parham P., Barnstable C. J., Bodmer W. F. Use of a monoclonal antibody (W6/32) in structural studies of HLA-A,B,C, antigens. J Immunol. 1979 Jul;123(1):342–349. [PubMed] [Google Scholar]
- Pellegrino M. A., Ng A. K., Russo C., Ferrone S. Heterogeneous distribution of the determinants defined by monoclonal antibodies on HLA-A and B antigens bearing molecules. Transplantation. 1982 Jul;34(1):18–23. doi: 10.1097/00007890-198207000-00004. [DOI] [PubMed] [Google Scholar]
- Ploegh H. L., Cannon L. E., Strominger J. L. Cell-free translation of the mRNAs for the heavy and light chains of HLA-A and HLA-B antigens. Proc Natl Acad Sci U S A. 1979 May;76(5):2273–2277. doi: 10.1073/pnas.76.5.2273. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Quaranta V., Walker L. E., Pellegrino M. A., Ferrone S. Purification of immunologically functional subsets of human Ia-like antigens on a monoclonal antibody (Q5/13) immunoadsorbent. J Immunol. 1980 Oct;125(4):1421–1425. [PubMed] [Google Scholar]
- Rognum T. O., Brandtzaeg P., Thorud E. Is heterogeneous expression of HLA-dr antigens and CEA along with DNA-profile variations evidence of phenotypic instability and clonal proliferation in human large bowel carcinomas? Br J Cancer. 1983 Oct;48(4):543–551. doi: 10.1038/bjc.1983.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ruiter D. J., Bergman W., Welvaart K., Scheffer E., van Vloten W. A., Russo C., Ferrone S. Immunohistochemical analysis of malignant melanomas and nevocellular nevi with monoclonal antibodies to distinct monomorphic determinants of HLA antigens. Cancer Res. 1984 Sep;44(9):3930–3935. [PubMed] [Google Scholar]
- Ruiter D. J., Bhan A. K., Harrist T. J., Sober A. J., Mihm M. C., Jr Major histocompatibility antigens and mononuclear inflammatory infiltrate in benign nevomelanocytic proliferations and malignant melanoma. J Immunol. 1982 Dec;129(6):2808–2815. [PubMed] [Google Scholar]
- 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]
- Selby W. S., Janossy G., Mason D. Y., Jewell D. P. Expression of HLA-DR antigens by colonic epithelium in inflammatory bowel disease. Clin Exp Immunol. 1983 Sep;53(3):614–618. [PMC free article] [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]
- Spratt J. S., Jr, Spjut H. J. Prevalence and prognosis of individual clinical and pathologic variables associated with colorectal carcinoma. Cancer. 1967 Nov;20(11):1976–1985. doi: 10.1002/1097-0142(196711)20:11<1976::aid-cncr2820201125>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
- Svennevig J. L., Lunde O. C., Holter J., Bjørgsvik D. Lymphoid infiltration and prognosis in colorectal carcinoma. Br J Cancer. 1984 Mar;49(3):375–377. doi: 10.1038/bjc.1984.60. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Symonds D. A., Vickery A. L. Mucinous carcinoma of the colon and rectum. Cancer. 1976 Apr;37(4):1891–1900. doi: 10.1002/1097-0142(197604)37:4<1891::aid-cncr2820370439>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
- Thorsby E., Bergholtz B., Berle E., Braathen L., Hirschberg H. Involvement of HLA in T-cell immune responses. Transplant Proc. 1981 Mar;13(1 Pt 2):903–908. [PubMed] [Google Scholar]
- Umpleby H. C., Heinemann D., Symes M. O., Williamson R. C. Expression of histocompatibility antigens and characterization of mononuclear cell infiltrates in normal and neoplastic colorectal tissues of humans. J Natl Cancer Inst. 1985 Jun;74(6):1161–1168. [PubMed] [Google Scholar]
- WOLFMAN E. F., Jr, ASTLER V. B., COLLER F. A. Mucoid adenocarcinoma of the colon and rectum. Surgery. 1957 Nov;42(5):846–852. [PubMed] [Google Scholar]
- Watt A. G., House A. K. Colonic carcinoma: a quantitative assessment of lymphocyte infiltration at the periphery of colonic tumors related to prognosis. Cancer. 1978 Jan;41(1):279–282. doi: 10.1002/1097-0142(197801)41:1<279::aid-cncr2820410139>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
- Weiss M. A., Michael J. G., Pesce A. J., DiPersio L. Heterogeneity of beta 2-microglobulin in human breast carcinoma. Lab Invest. 1981 Jul;45(1):46–57. [PubMed] [Google Scholar]
- van den Ingh H. F., Griffioen G., Cornelisse C. J. Flow cytometric detection of aneuploidy in colorectal adenomas. Cancer Res. 1985 Jul;45(7):3392–3397. [PubMed] [Google Scholar]