Immune evasion in colo-rectal cancer in a cohort of Sudanese patients: possible roles for MHC Class II antigens

 
 
 
  • Abstract
  • Keywords
  • References
  • PDF
  • Abstract


    Background: Colorectal cancer (CRC) is the third most common cancer world-wide. The majority of cases occur in the developed world. This prospective study aimed to correlate different human leukocyte antigens (HLA types; HLA DRB1 and DRB3) with the aggressiveness of CRC in Sudanese patients.

    Methods: Thirty-three patients with histopathologically confirmed CRC were included in the study. Demographic, clinical and laboratory data were recorded. Molecular typing for HLA DRB1 (DR1, 7 and 17), DRB3 and DRB4 were carried out using PCR-based Sequence-Specific Primers.

    Results: Forty percent of the patients were ≤ 50years; with a male to female ratio of 2.5:1. Rectal bleeding was the commonest presenting symptom. While moderately differentiated adenocarcinoma was the dominant histological type. Duke's stages B and C were reported in 54.6% and 42.4% of patients, respectively. No patients presented with Dukes stages A or D. HLA DRB3 was the most frequent allele detected followed by DRB4 and DR17. A higher frequency of the DRB3 allele was found in the peripheral blood when compared with the tumor and apparently normal tissues. HLA DRB3 and DR7 allele frequencies correlated with Duke's stages B and C but not with age, sex or degree of differentiation, while blood DR17 antigen correlated only with the degree of tumor differentiation.

    Conclusion: CRC was found to have a higher occurrence in younger patients.  Tumors were aggressive with advance Duke's stage at presentation. This aggressive nature could possibly be related to either increased HLA DRB3 or DR7 or decreased HLA DR17 levels in the tumor tissue when compared with the blood. No differences between tumor and normal colon tissues were found, in concordance with the multifocally of colon cancer theory.


  • Keywords


    Aggressive Colo-Rectal Cancer; MHC Class II Antigens; Sudan.

  • References


      [1] World Health Organization. The Global Burden of Disease: 2004 Update. Geneva: World Health Organization 2008. https://doi.org/10.3322/caac.20138.

      [2] Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012 Jan-Feb; 62:10-29. doi: 10.3322/caac.20138.

      [3] Matanoski G, Tao X, Almon L, Adade AA, Davies-Cole JO. Demographics and tumor characteristics of colorectal cancers in the United States, 1998-2001. Cancer. 2006; 107: 1112-1120. https://doi.org/10.1002/cncr.22008.

      [4] Saeed E I, Hsin-Yi Weng, Mohamed K H and Mohammed SI. Cancer incidence in Khartoum, Sudan: first results from the Cancer Registry, 2009–2010. Cancer Med 2014 Aug; 3: 1075–1084. doi: 10.1002/cam4.254. https://doi.org/10.1002/cam4.254.

      [5] Menon AG, Janssen-van Rhijn CM, Morreau H, Putter H, Tollenaar RA, van de Velde CJ, Fleuren GJ, Kuppen PJ. Immune system and prognosis in colorectal cancer: a detailed immunohistochemical analysis. Lab Invest 2004; 84: 493–501. https://doi.org/10.1038/labinvest.3700055.

      [6] Cavallo F, De GC, Nanni P, Forni G, Lollini PL. The immune hallmarks of cancer. Cancer Immunol Immunother 2011; 60: 319–326. https://doi.org/10.1007/s00262-010-0968-0.

      [7] Shunyakov L, Ryan CK, Sahasrabudhe DM, Khorana AA. The influence of host response on colorectal cancer prognosis. Clin Colorectal Cancer 2004; 1:38–45. https://doi.org/10.3816/CCC.2004.n.008.

      [8] Giuseppe VM, Emilia Andersson, Lisa Villabona, Hildur Helgadottir ,Kjell Bergfeldt, Federica Cavallo, et al. Survival of the fittest or best adapted: HLA-dependent tumor development. Journal of Nucleic Acids Investigation 2010; 10.4081. doi:10.4081/jnai.2010.

      [9] Giuseppe S, Serenella E, Inti Z, Eva K, Roberto A, Andrea C, Sara Caratelli et.al. HLA Class II Antigen Expression in Colorectal Carcinoma Tumors as a Favorable Prognostic Marker. Neoplasia 2014 Jan; 16: 31–42.doi.org/10.1593/neo.131568.

      [10] Daar AS, Fuggle SV, Fabre JW, Ting A, Morris PJ. The detailed distribution of MHC class II antigens in normal human organs. Transplantation1984; 38:293. https://doi.org/10.1097/00007890-198409000-00019.

      [11] De Bruin EC, van de Velde CJ, van Krieken JH, Marijnen CA, and Medema JP. Epithelial human leukocyte antigen-DR expression predicts reduced recurrence rates and prolonged survival in rectal cancer patients. Clin Cancer Res 2008; 14, 1073–1079. https://doi.org/10.1158/1078-0432.CCR-07-1597.

      [12] Lazzaro B, Anderson AE, Kajdacsy-Balla A, and Hessner MJ. Antigenic characterization of medullary carcinoma of the breast: HLA-DR expression in lymph node positive cases. Appl Immunohistochem Mol Morphol 2001; 9, 234–241. https://doi.org/10.1097/00129039-200109000-00007.

      [13] Taramelli D, Fossati G, Mazzocchi A, Delia D, Ferrone S, and Parmiani G. Classes I and II HLA and melanoma-associated antigen expression and modulation on melanoma cells isolated from primary and metastatic lesions. Cancer Res 1986; 46, 433–439.

      [14] Lovig T, Andersen SN, Thorstensen L, Diep CB, Meling GI, Lothe RA, and Rognum TO. Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis. Br J Cancer 2006; 87, 756–762. https://doi.org/10.1038/sj.bjc.6600507.

      [15] Moller P, Momburg F, Koretz K, Moldenhauer G, Herfarth C, Otto HF, Hämmerling GJ and Schlag P. Influence of major histocompatibility complex class I and II antigens on survival in colorectal carcinoma. Cancer Res 1991; 51, 729 –736.

      [16] Mulder WM, Stern PL, Stukart MJ, de Windt E, Butzelaar RM, Meijer S, et al. Low intercellular adhesion molecule 1 and high 5T4 expression on tumor cells correlate with reduced disease-free survival in colorectal carcinoma patients. Clin Cancer Res 1997; 3, 1923–1930.

      [17] Diederichsen AC, Hjelmborg J, Christensen PB, Zeuthen J, and Fenger C. Prognostic value of the CD4+/CD8+ ratio of tumour infiltrating lymphocytes in colorectal cancer and HLA-DR expression on tumour cells. Cancer Immunol Immunother 2003; 52, 423 –428. https://doi.org/10.1007/s00262-003-0388-5.

      [18] Bruce A Roe, Judy S. Crabtreeand Akbar S. Khan, DNA Isolation and Sequencing in Essential Techniques Series 1996, Published by John Wiley & Sons, ISBN 0-471-97324.

      [19] Janeway CA Jr, Travers P, Walport M, Shlomchik M J. functions”. In Immunobiology, 5th edn,New York: Garland Science, 2001.

      [20] Wintzer HO, Benzing M, von Kleist S. Lacking prognostic significance of 2-microglobulin, MHC class I and class II antigen expression in breast carcinomas. BrJ Cancer 1990; 289–295. https://doi.org/10.1038/bjc.1990.280.

      [21] Goepel JR, Rees RC, Rogers K, Stoddard CJ, Thomas WEG, Shepherd L. Loss of monomorphic and polymorphic HLA antigens in metastatic breast and colon carcinoma. Br J Cancer 1991; 880–883. https://doi.org/10.1038/bjc.1991.418.

      [22] Gao R N, Neutel C I, Wai E. Gender differences in colorectal cancer incidence, mortality, hospitalization and surgical procedures in Canada. J Public health 2008.30:194-201. https://doi.org/10.1093/pubmed/fdn019.

      [23] Abotchie PN, Vernon SW, Du XL. Gender differences in colorectal cancer incidence in the United State, 1975-2006. J Women’s Health 2012; 21: 393-400. https://doi.org/10.1089/jwh.2011.2992.

      [24] Rath-Wolfson, L O, Purim O, Ram E, Morgenstern S, Koren R, Brenner B. "Expression of estrogen receptor beta1 in colorectal cancer: correlation with clinicopathological variables." Oncol Rep 2012; 27: 2017-2022. https://doi.org/10.3892/or.2012.1712.

      [25] Koo J H & Rupert WL. Sex differences in epidemiological, clinical and pathological characteristics of colorectal cancer. Journal of Gastroenterology and Hepatology 2010; 33–42.

      [26] Majek O, Gondos A, Jansen L, Emrich K, Holleczek B, Katalinic A, et al. Sex Differences in Colorectal Cancer Survival: Population-Based Analysis of 164,996 Colorectal Cancer Patients in Germany. PLoS ONE 2013; 8: e68077. https://doi.org/10.1371/journal.pone.0068077.

      [27] Zahir M N, Azhar E M, Rafig S, Ghias K and Shabbir M. Clinical features and outcome of sporadic colorectal carcinoma in young patients: a cross sectional analysis from developing country. ISRN Oncol 2014; 46-1570. https://doi.org/10.1155/2014/461570.

      [28] Wang R, Wang M J & Pinge J. Clinicopathological Features and Survival Outcomes of Colorectal Cancer in Young versus Elderly: A Population-Based Cohort Study of SEER 9 Registries Data (1988–2011) Medicine (Baltimore) 2015; 94: e1402. https://doi.org/10.1097/MD.0000000000001402.

      [29] Taha MO, Abdalla AA, and Mohamed R S. Pattern & presentation of colorectal cancer in central Sudan, a retrospective descriptive study, 2010–2012, Afr Health Sci 2015; 15: 576–580. https://doi.org/10.4314/ahs.v15i2.3.

      [30] Mohammed MM, Musaad A M, Eltayeb E and Abdalaziz M. Colorectal Carcinoma in Sudanese Patients. International Journal of Medicine 2015; 3: 98-102. https://doi.org/10.14419/ijm.v3i2.5159.

      [31] Abdalla A A, Musa MT & Khair R Z. Presentation of Colorectal Cancer in Khartoum Teaching Hospital.Sudan JMS 2007; 2: 263-65.

      [32] Adesanya AA, da Rocha-Afodu JT. Colorectal cancer in Lagos: a critical review of 100 cases. Niger Postgrad Med J 2000; 7: 129–136. https://doi.org/10.3748/wjg.14.6531.

      [33] Matsushita K, Takenouchi T, Kobayashi S, Hayashi H, Okuyama K, Ochiai T et al. HLA-DR antigen expression in colorectal carcinomas: influence of expression by IFN-γ in situ and its association with tumour progression. Br J Cancer 1996; 73: 644–8.

      [34] Zeh HJ, Stavely-O’Carroll K, Choti MA. Vaccines for colorectal cancer. Trends Mol Med 2001; 7: 307–13.doi.org/10.1016/S1471-4914 (01)01992-X.

      [35] Mayer L, Eisenhardt D, Salomon P, Bauer W, Plous R, Piccinini L. Expression of class II molecules on intestinal epithelial cells in humans. Differences between normal and inflammatory bowel disease. Gastroenterology 1991; 100: 3–12. https://doi.org/10.1016/0016-5085(91)90575-6.

      [36] Satoh A, Toyota M, Ikeda H, Morimoto Y, Akino K, Mita H et al. Epigenetic inactivation of class II transactivator (CIITA) is associated with the absence of interferongamma- induced HLA-DR expression in colorectal and gastric cancer cells. Oncogene 2004; 23: 8876–86. https://doi.org/10.1038/sj.onc.1208144.

      [37] McDougall CJ, Ngoi SS, Goldman IS, Godwin T, Felix J, DeCosse JJ, et al. Reduced Expression of HLA Class I and II Antigens in Colon Cancer. CANCER RESEARCH 1990; 50: 8023-8027.

      [38] Masahiro Iizuka, Mitsuro Chiba, Yasuo Horie, Osamu Masamune and Hiromasa Ohta. Lymphoid cell subsets in colonie mucosa and HLA-DR antigens on colonic epithelia in colitis excluding ulcerative colitis and crohn’s disease. Gastroenterologia Japonica 1990; 25-700.

      [39] Matsushita K, Takenouchi T, Shimada H, Tomonaga T, Hayashi H, Shioya A, et al. "Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients: Possible involvement of c-myc suppression by interferon-gamma in situ. Cancer Sci 2006; 57-63.

      [40] Tamiolakis D, Venizelos J, Papadopoulos N, Lambropoulou M, Papadopoulos E, Simopoulos C. Expression of HLA-DR antigen and characterization of the lymphocytic infiltrate in normal mucosa, tubullovillous adenoma and invasive carcinoma of the colon. Chirurgia 2005; 100: 451-456.

      [41] Dierssen JW, de Miranda NF, Mulder A, van Puijenbroek M, Verduyn W, Claas FH, et.al. High resolution analysis of HLA class I alterations in colorectal cancer. BMC Cancer 2006; 6: 233. https://doi.org/10.1186/1471-2407-6-233.

      [42] Facista A, Nguyen H, Lewis C, Prasad AR, Ramsey L, Zaitlin B, et al. Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer. Genome Integr. 2012; 11:3:3. https://doi.org/10.1186/2041-9414-3-3.


 

View

Download

Article ID: 7995
 
DOI: 10.14419/ijm.v5i2.7995




Copyright © 2012-2015 Science Publishing Corporation Inc. All rights reserved.