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Significance of immunohistochemical overexpression of cyclooxygenase-2 in overall and disease-free survival of oral squamous cell carcinoma patients

  • S M Adnan Ali (a1), S Naeem (a1), Y Mirza (a1), N Zahid (a1) and M S Awan (a2)...
Abstract
Objective

In Pakistan, oral cancer ranks as the most common malignancy in males and the second most common malignancy in females. Cyclooxygenase-2 has been explored as an agent of carcinogenesis in oral and other neoplasms. This study aimed to observe the expression of cyclooxygenase-2 in oral squamous cell carcinoma, and to correlate the expression with patients’ clinical features and overall and disease-free survival.

Methods

Immunohistochemistry for cyclooxygenase-2 was performed on a total of 100 oral squamous cell carcinoma formalin-fixed, paraffin-embedded blocks. Expression was correlated with patients’ clinicopathological variables and overall and disease-free survival.

Results

Cyclooxygenase-2 was overexpressed in 55 per cent of oral squamous cell carcinoma patients. Overexpression was correlated with overall survival (p = 0.013) and disease-free survival (p = 0.001) on univariate analysis. However, on multivariate analysis, cyclooxygenase-2 was associated with only disease-free survival (p = 0.044) and not overall survival (p = 0.208).

Conclusion

Expression of cyclooxygenase-2 is associated with poorer overall survival and higher rates of recurrence in oral squamous cell carcinoma patients.

Copyright
Corresponding author
Author for correspondence: Dr Syed Muhammad Adnan Ali, Department of Surgery, Aga Khan University Hospital, Stadium Road, PO Box 3500, Karachi 74800, Pakistan E-mail: syed.adnan@aku.edu Fax: +92 21 3493 4294
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Dr S M Adnan Ali takes responsibility for the integrity of the content of the paper

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References
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1Jemal, A, Bray, F, Center, MM, Ferlay, J, Ward, E, Forman, D. Global cancer statistics. CA Cancer J Clin 2011;61:6990
2Aamir, S, Mirza, T, Mirza, MA, Qureshi, M. Emerging patterns in clinico-pathological spectrum of oral cancers. Pak J Med Sci 2013;29:783–7
3Ferlay, J, Soerjomataram, I, Dikshit, R, Eser, S, Mathers, C, Rebelo, M et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E35986
4Joshi, P, Dutta, S, Chaturvedi, P, Nair, S. Head and neck cancers in developing countries. Rambam Maimonides Med J 2014;5:e0009
5Parkin, DM, Arslan, A, Bieber, A, Bouvy, O, Muir, C, Owor, R et al. Cancer Occurrence in Developing Countries. Lyon: IARC, 1986
6Bhurgri, Y, Bhurgri, A, Hussainy, AS, Usman, A, Faridi, N, Malik, J et al. Cancer of the oral cavity and pharynx in Karachi--identification of potential risk factors. Asian Pac J Cancer Prev 2003;4:125–30
7Alamgir, MM, Jamal, Q, Mirza, T. Conventional clinical and prognostic variables in 150 oral squamous cell carcinoma cases from the indigenous population of Karachi. Pak J Med Sci 2016;32:672–6
8Farrukh, S, Syed, S, Pervez, S. Differential expression of cytokeratin 13 in non-neoplastic, dysplastic and neoplastic oral mucosa in a high risk Pakistani population. Asian Pac J Cancer Prev 2015;16:5489–92
9Martinez-Useros, J, Garcia-Foncillas, J. The challenge of blocking a wider family members of EGFR against head and neck squamous cell carcinomas. Oral Oncol 2015;51:423–30
10Bhurgri, Y. Cancer of the oral cavity--trends in Karachi South (1995–2002). Asian Pac J Cancer Prev 2005;6:22–6
11Amirchaghmaghi, M, Mohtasham, N, Mozaffari, PM. Comparison of COX2 expression between oral squamous cell carcinoma, leukoplakia and normal mucosa. J Contemp Dent Pract 2012;13:205–9
12Wang, Z-M, Liu, J, Liu, H-B, Ye, M, Zhang, Y-F, Yang, D-S. Abnormal COX2 protein expression may be correlated with poor prognosis in oral cancer: a meta-analysis. Biomed Res Int 2014;2014:364207
13Williams, CS, Mann, M, DuBois, RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 1999;18:7908–16
14Dannenberg, AJ, Altorki, NK, Boyle, JO, Dang, C, Howe, LR, Weksler, BB et al. Cyclo-oxygenase 2: a pharmacological target for the prevention of cancer. Lancet Oncol 2001;2:544–51
15Bartchewsky, W Jr, Martini, MR, Masiero, M, Squassoni, AC, Alvarez, MC, Ladeira, MS et al. Effect of Helicobacter pylori infection on IL-8, IL-1β and COX-2 expression in patients with chronic gastritis and gastric cancer. Scand J Gastroenterol 2009;44:153–61
16Harris, R. Cyclooxygenase-2 (cox-2) blockade in the chemoprevention of cancers of the colon, breast, prostate, and lung. Inflammopharmacology 2009;17:5567
17Kim, Y-Y, Lee, E-J, Kim, Y-K, Kim, S-M, Park, J-Y, Myoung, H et al. Anti-cancer effects of celecoxib in head and neck carcinoma. Mol Cells 2010;29:185–94
18Looby, E, Abdel-Latif, MM, Athié-Morales, V, Duggan, S, Long, A, Kelleher, D. Deoxycholate induces COX-2 expression via Erk1/2-, p38-MAPK and AP-1-dependent mechanisms in esophageal cancer cells. BMC Cancer 2009;9:190
19Ratnasinghe, D, Tangrea, J, Roth, M, Dawsey, S, Hu, N, Anver, M et al. Expression of cyclooxygenase-2 in human squamous cell carcinoma of the esophagus; an immunohistochemical survey. Anticancer Res 1998;19:171–4
20Tucker, ON, Dannenberg, AJ, Yang, EK, Zhang, F, Teng, L, Daly, JM et al. Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res 1999;59:987–90
21Wang, X, Colby, JK, Rengel, RC, Fischer, SM, Clinton, SK, Klein, RD. Overexpression of cyclooxygenase-2 (COX-2) in the mouse urinary bladder induces the expression of immune- and cell proliferation-related genes. Mol Carcinog 2009;48:113
22Pandey, M, Prakash, O, Santhi, W, Soumithran, C, Pillai, R. Overexpression of COX-2 gene in oral cancer is independent of stage of disease and degree of differentiation. Int J Oral Maxillofac Surg 2008;37:379–83
23Cao, X, Zhang, S, Wu, H, Liu, X, Zhang, Y. Relationship between the expression of cyclooxygenase-2 and microvessel density in oral squamous cell carcinoma [in Chinese]. Hua xi Kou Qiang Yi Xue Za Zhi 2005;23:431–3
24Mohammad, S, Ram, H, Gupta, PN, Husain, N, Bhatt, M. Overexpression of COX-2 in oral squamous cell carcinoma patients undergoing chemoradiotherapy. Natl J Maxillofac Surg 2011;2:1721
25Scully, C, Field, J, Tanzawa, H. Genetic aberrations in oral or head and neck squamous cell carcinoma (SCCHN): 1. Carcinogen metabolism, DNA repair and cell cycle control. Oral Oncol 2000;36:256–63
26Altman, DG, McShane, LM, Sauerbrei, W, Taube, SE. Reporting recommendations for tumor marker prognostic studies (REMARK): explanation and elaboration. BMC Med 2012;10:51
27Shibata, M, Kodani, I, Osaki, M, Araki, K, Adachi, H, Ryoke, K et al. Cyclo-oxygenase-1 and -2 expression in human oral mucosa, dysplasias and squamous cell carcinomas and their pathological significance. Oral Oncol 2005;41:304–12
28Nankivell, P, Williams, H, McConkey, C, Webster, K, High, A, MacLennan, K et al. Tetraspanins CD9 and CD151, epidermal growth factor receptor and cyclooxygenase-2 expression predict malignant progression in oral epithelial dysplasia. Br J Cancer 2013;109:2864–74
29Alamgir, M, Jamal, Q, Jafarey, N, Mirza, T. Clinicopathological parameters of 50 oral squamous cell carcinoma cases in Karachi. Pak J Med Dent 2013;2:38
30Haffner, MC, Laimer, J, Chaux, A, Schäfer, G, Obrist, P, Brunner, A et al. High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity. Mod Pathol 2012;25:1079–85
31Cha, JD, Li, S, Cha, IH. Association between expression of embryonic lethal abnormal vision-like protein HuR and cyclooxygenase-2 in oral squamous cell carcinoma. Head Neck 2011;33:627–37
32Itoh, S, Matsui, K, Furuta, I, Takano, Y. Immunohistochemical study on overexpression of cyclooxygenase-2 in squamous cell carcinoma of the oral cavity: its importance as a prognostic predictor. Oral Oncol 2003;39:829–35
33Moraitis, D, Du, B, De Lorenzo, MS, Boyle, JO, Weksler, BB, Cohen, EG et al. Levels of cyclooxygenase-2 are increased in the oral mucosa of smokers: evidence for the role of epidermal growth factor receptor and its ligands. Cancer Res 2005;65:664–70
34Huang, R-Y, Chen, GG. Cigarette smoking, cyclooxygenase-2 pathway and cancer. Biochim Biophys Acta 2011;1815:158–69
35Juuti, A, Louhimo, J, Nordling, S, Ristimäki, A, Haglund, C. Cyclooxygenase-2 expression correlates with poor prognosis in pancreatic cancer. J Clin Pathol 2006;59:382–6
36Athanassiadou, P, Grapsa, D, Athanassiades, P, Gonidi, M, Athanassiadou, A-M, Tsipis, A et al. The prognostic significance of COX-2 and survivin expression in ovarian cancer. Pathol Res Pract 2008;204:241–9
37Hida, T, Yatabe, Y, Achiwa, H, Muramatsu, H, Kozaki, K, Nakamura, S et al. Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res 1998;58:3761–4
38Ranelletti, FO, Almadori, G, Rocca, B, Ferrandina, G, Ciabattoni, G, Habib, A et al. Prognostic significance of cyclooxygenase-2 in laryngeal squamous cell carcinoma. Int J Cancer 2001;95:343–9
39Renkonen, J, Wolff, H, Paavonen, T. Expression of cyclo-oxygenase-2 in human tongue carcinoma and its precursor lesions. Virchows Arch 2002;440:594–7
40Nozoe, T, Ezaki, T, Kabashima, A, Baba, H, Maehara, Y. Significance of immunohistochemical expression of cyclooxygenase-2 in squamous cell carcinoma of the esophagus. Am J Surg 2005;189:110–15
41Toyoshima, T, Kamijo, R, Takizawa, K, Sumitani, K, Ito, D, Nagumo, M. Inhibitor of cyclooxygenase-2 induces cell-cycle arrest in the epithelial cancer cell line via up-regulation of cyclin dependent kinase inhibitor p21. Br J Cancer 2002;86:1150–6
42Zhang, S, Bian, H, Li, X, Wu, H, Bi, Q, Yan, Y et al. Hydrogen sulfide promotes cell proliferation of oral cancer through activation of the COX2/AKT/ERK1/2 axis. Oncol Rep 2016;35:2825–32
43Chandrasekharan, N, Simmons, DL. The cyclooxygenases. Genome Biol 2004;5:241
44Johnson, GE, Ivanov, VN, Hei, TK. Radiosensitization of melanoma cells through combined inhibition of protein regulators of cell survival. Apoptosis 2008;13:790802
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The Journal of Laryngology & Otology
  • ISSN: 0022-2151
  • EISSN: 1748-5460
  • URL: /core/journals/journal-of-laryngology-and-otology
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