Immunohistochemical detection of Def6 protein in oral cancer
DOI:
https://doi.org/10.11113/mjfas.v15n5.1496Keywords:
Def6, immunohistochemistry, oral cancer, protein expressionAbstract
Nowadays oral cancer had become global health issue and reach 21st rank in Malaysian population. Def6 or IRF-4-binding proteins (IBP) that are mostly produced in lymph node and thymus are associated with cell survival and cell proliferation. Def6 protein expression is often found in autoimmune diseases, but current studies also found Def6 in some cancers. In this study, we would like to detect Def6 protein expression in oral cancer. 36 formalin-fixed paraffin embedded tissue were selected for both test group (oral cancer) and control group (normal oral mucosa). The cases were retrieved from the archives of faculty of dentistry, University of Malaya, Kuala Lumpur. Immunohistochemistry (IHC) staining was manually performed using Def6 antibody (Abcam 1:300) and assessed quantitatively (positivity and staining intensity). Positive and negative controls were used to validate the IHC run. All data were then analysed using SPSS version 25.0. Control group is negative for Def6 expression. 29 cases (82.86%) of oral cancer were Def6 positive with 2.86% weak staining, 5.71% moderate staining and 74.28% had strong staining intensity. There is significant different between Def6 expression in normal oral mucosa and oral cancer (p<0.05). Thus, we postulate that Def6 expression plays a big role in carcinogenesis of human oral cancer.
References
Barnes, L., Eveson, J. W., Reichart, P., Sidransky, D. 2005. Pathology and genetics of head and neck tumours. Geneva, Switzerland: WHO Press.
Binder, N., Miller, C., Yoshida, M., Inoue, K., Nakano, S., Hu, X., Ivashkiv, L. B. Schett, G., Pernis, A., Goldring, S. R., Ross, F. P. Zhao, B. 2017. Def6 Restrains Osteoclastogenesis and Inflammatory
Bone Resorption. J. Immunol. 198(9).
Canonigo-Balancio, A. J., Fos, C., Prod’homme, T., Bécart, S., Altman, A. 2009. SLAT/Def6 plays a critical role in the development of Th17 cell- mediated experimental autoimmune encephalomyelitis. J. Immunol. 183(11), 7259–7267.
Chandrasekaran, U., Yi, W., Gupta, S., Weng, C. H., Giannopoulou, E., Chinenov, Y., Jessberger, R., Weaver, C. T., Bhagat, G., Pernis, A. B. 2016. Regulation of effector tregs in murine lupus. Arthritis Rheumatol. 68(6), 1454-1466.
Fanzo, J. C., Yang, W., So, Y. J., Gupta, S., Chen, Q., Siddiq, A., Greenberg, S. Pernis, A. B. 2006. Loss of IRF-4-binding protein leads to the spontaneous development of systemic autoimmunity. J. Clin. Invest. 116(3), 703–714.
Gupta, S., Lee, A., Hu, C., Fanzo, J., Goldberg, I., Cattoretti, G. Pernis, A. B. 2003. Molecular cloning of IBP, a SWAP-70 homologous GEF, which is highly expressed in the immune system. Human Immunol. 64(4), 389–401.
Hashimoto, M., Nagao, J. I., Ikezaki, S., Tasaki, S., Arita-Morioka, K. I., Narita, Y., Cho, T. Yuasa, K., Altman, A., Tanaka, Y. 2017. Identification of a novel alternatively spliced form of inflammatory regulator SWAP-70-like adapter of T cells. Int. J. Inflam. 2017.
Jian, C.-X., Yang, M.-Z., Li, P., Xiong, J., Zhang, Z.-J., Li, C.-J., Chen, A., Hu, C. M., Zhou, J. X., Li, S. H. 2012. Ectopically expressed IBP promotes cell proliferation in oral squamous cell carcinoma. Cancer Invest. 30(10), 748–756.
Joshi, R. N., Binai, N. A., Marabita, F., Sui, Z., Altman, A., Heck, A. J. R., Tegnér, J. Schmidt, A. 2017. Phosphoproteomics reveals regulatory T cell-mediated DEF6 dephosphorylation that affects cytokine expression in human conventional T cells. Frontiers Immunol. 25(8), 1163.
Khor, G. H., Froemming, G. R. A., Zain, R. B., Abraham, M. T., Thong, K. L. 2014. Screening of differential promoter hypermethylated genes in primary oral squamous cell carcinoma. Asian Pacific J. Cancer Prev. 15(20), 8957-8961.
Li, P., Zhang, Z., Wang, Q., Li, S., Zhang, Y., Bian, X., Chen, A. Hu, C. 2009. The ectopic expression of IFN regulatory factor 4-binding protein is correlated with the malignant behavior of human breast cancer cells. J. Int. Immunopharmacol. 9(7–8), 1002–1009.
Liew, P.-L., Fang, C.-Y., Lee, Y.-C., Lee, Y.-C., Chen, C.-L., Chu, J.-S. 2016. DEF6 expression in ovarian carcinoma correlates with poor patient survival. Diagn. Pathol. 11(1), 68.
Liu, S., Liu, D., Li, J., Zhang, D., Chen, Q. 2016. Regulatory T cells in oral squamous cell carcinoma. J. Oral Pathol. Med. 45(9), 635-639.
Montero, P. H., Patel, S. G. 2015. Cancer of the oral cavity. Surg Oncol Clin. N. Am. 24(3), 491-508.
Neville, B. W., Damm, D. D., Allen, C. M. & Chi, A. C. 2016. Oral and maxillofacial pathology, 4th ed. Missouri: Elsevier.
Ni, A., Chen, H., Wu, Y., Li, W., Chen, S., Li, J. 2012. Expression of IRF-4 and IBP in skin lesions of patients with psoriasis vulgaris. J Huazhong Univ. Sci. Technolog. Med. Sci. 32(2), 287–90.
Odell, E. 2017. Cawson’s essentials of oral pathology and oral medicine, 9th ed. Missouri: Elsevier.
Otsubo, T., Hida, Y., Ohga, N., Sato, H., Kai, T., Matsuki, Y., Takasu, H., Akiyama, K., Maishi, N., Kawamoto, T., Shinohara, N., Nonomura, K., Hida, K. 2014. Identification of novel targets for antiangiogenic therapy by comparing the gene expressions of tumor and normal endothelial cells. Cancer Sci. 105(5), 560-567.
Rhodus, N. L., Kerr, A. R., Patel, K. 2014. Oral cancer. leukoplakia, premalignancy, and squamous cell carcinoma. Dent. Clin. North Am. 58(2), 315-340.
Rivera, C. 2015. Essentials of oral cancer. Int. J. Clin. Exp. Pathol. 8(9), 11884-11894.
Stock, M. L., Peterson, L. M., Houlihan, A. E., Walsh, L. A. 2013. Influence of oral sex and oral cancer information on young adults’ oral sexual-risk cognitions and likelihood of HPV vaccination. J. Sex Res. 50(1), 95–102.
Subramanian, S., West, R. B., Marinelli, R. J., Nielsen, T. O., Rubin, B. P., Goldblum, J. R., Patel, R. M., Zhu, S., Montgomery, K., Ng, T. L., Corless, C. L., Heinrich, M .C., Van de Rijn, M. 2005. The gene expression profile of extraskeletal myxoid chondrosarcoma. J. Pathol. 206(4), 433-444.
Vistica, B. P., Shi, G., Nugent, L., Tan, C., Altman, A., Gery, I. 2012. SLAT/Def6 plays a critical role in the pathogenic process of experimental autoimmune uveitis (EAU). Mol. vis. 18, 1858–64. Retrieved from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid= 3398495&tool=pmcen trez&rendertype=abstract.
Yi, W., Gupta, S., Ricker, E., Manni, M., Jessberger, R., Chinenov, Y., Molina, H., Pernis, A. B. 2017. The mTORC1-4E-BP-eIF4E axis controls de novo Bcl6 protein synthesis in T cells and systemic autoimmunity. Nat. Commun. 8(1), 254.
Zhang, Z., Wang, Q., Li, P., Zhou, Y., Li, S., Yi, W., Chen, A., Kong, P., Hu, C. 2009. Overexpression of the interferon regulatory factor 4-binding protein in human colorectal cancer and its clinical significance. Cancer Epidemiol. 33(2), 130–136.
Zhang, Z., Yang, M., Chen, R., Su, W., Li, P., Chen, S., Chen, Z. Li, S., Hu, C. 2014. IBP regulates epithelial-to-mesenchymal transition and the motility of breast cancer cells via Rac1, RhoA and Cdc42 signaling pathways. Oncogene 33(26), 3374–3382.
