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

Published online by Cambridge University Press:  24 January 2019

S M Adnan Ali ,
S Naeem ,
Y Mirza ,
N Zahid  and
M S Awan
S M Adnan Ali*
Affiliation:
Department of Surgery, Aga Khan University Hospital, Karachi, Pakistan
S Naeem
Affiliation:
Department of Surgery, Aga Khan University Hospital, Karachi, Pakistan
Y Mirza
Affiliation:
Department of Surgery, Aga Khan University Hospital, Karachi, Pakistan
N Zahid
Affiliation:
Department of Surgery, Aga Khan University Hospital, Karachi, Pakistan
M S Awan
Affiliation:
Section of Otolaryngology – Head and Neck Surgery, Department of Surgery, Aga Khan University Hospital, Karachi, Pakistan
*
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: [email protected] Fax: +92 21 3493 4294
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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.

Keywords

Cyclooxygenase 2Oral CavityImmunohistochemistrySquamous Cell CarcinomaPrognosisDisease-Free Survival
Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 132 , Issue 12 , December 2018 , pp. 1102 - 1109
Copyright
Copyright © JLO (1984) Limited, 2019 

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Footnotes

Dr S M Adnan Ali takes responsibility for the integrity of the content of the paper

References

1Jemal, A, Bray, F, Center, MM, Ferlay, J, Ward, E, Forman, D. Global cancer statistics. CA Cancer J Clin 2011;61:69–90Google Scholar
2Aamir, S, Mirza, T, Mirza, MA, Qureshi, M. Emerging patterns in clinico-pathological spectrum of oral cancers. Pak J Med Sci 2013;29:783–7Google Scholar
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:E359–86Google Scholar
4Joshi, P, Dutta, S, Chaturvedi, P, Nair, S. Head and neck cancers in developing countries. Rambam Maimonides Med J 2014;5:e0009Google Scholar
5Parkin, DM, Arslan, A, Bieber, A, Bouvy, O, Muir, C, Owor, R et al. Cancer Occurrence in Developing Countries. Lyon: IARC, 1986Google Scholar
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;4:125–30Google Scholar
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;32:672–6Google Scholar
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;16:5489–92Google Scholar
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;51:423–30Google Scholar
10Bhurgri, Y. Cancer of the oral cavity--trends in Karachi South (1995–2002). Asian Pac J Cancer Prev 2005;6:22–6Google Scholar
11Amirchaghmaghi, M, Mohtasham, N, Mozaffari, PM. Comparison of COX2 expression between oral squamous cell carcinoma, leukoplakia and normal mucosa. J Contemp Dent Pract 2012;13:205–9Google Scholar
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;2014:364207Google Scholar
13Williams, CS, Mann, M, DuBois, RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 1999;18:7908–16Google Scholar
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;2:544–51Google Scholar
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;44:153–61Google Scholar
16Harris, R. Cyclooxygenase-2 (cox-2) blockade in the chemoprevention of cancers of the colon, breast, prostate, and lung. Inflammopharmacology 2009;17:55–67Google Scholar
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;29:185–94Google Scholar
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;9:190Google Scholar
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;19:171–4Google Scholar
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;59:987–90Google Scholar
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;48:1–13Google Scholar
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;37:379–83Google Scholar
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;23:431–3Google Scholar
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;2:17–21Google Scholar
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;36:256–63Google Scholar
26Altman, DG, McShane, LM, Sauerbrei, W, Taube, SE. Reporting recommendations for tumor marker prognostic studies (REMARK): explanation and elaboration. BMC Med 2012;10:51Google Scholar
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;41:304–12Google Scholar
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;109:2864–74Google Scholar
29Alamgir, M, Jamal, Q, Jafarey, N, Mirza, T. Clinicopathological parameters of 50 oral squamous cell carcinoma cases in Karachi. Pak J Med Dent 2013;2:3–8Google Scholar
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;25:1079–85Google Scholar
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;33:627–37Google Scholar
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;39:829–35Google Scholar
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;65:664–70Google Scholar
34Huang, R-Y, Chen, GG. Cigarette smoking, cyclooxygenase-2 pathway and cancer. Biochim Biophys Acta 2011;1815:158–69Google Scholar
35Juuti, A, Louhimo, J, Nordling, S, Ristimäki, A, Haglund, C. Cyclooxygenase-2 expression correlates with poor prognosis in pancreatic cancer. J Clin Pathol 2006;59:382–6Google Scholar
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;204:241–9Google Scholar
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;58:3761–4Google Scholar
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;95:343–9Google Scholar
39Renkonen, J, Wolff, H, Paavonen, T. Expression of cyclo-oxygenase-2 in human tongue carcinoma and its precursor lesions. Virchows Arch 2002;440:594–7Google Scholar
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;189:110–15Google Scholar
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;86:1150–6Google Scholar
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;35:2825–32Google Scholar
43Chandrasekharan, N, Simmons, DL. The cyclooxygenases. Genome Biol 2004;5:241Google Scholar
44Johnson, GE, Ivanov, VN, Hei, TK. Radiosensitization of melanoma cells through combined inhibition of protein regulators of cell survival. Apoptosis 2008;13:790–802Google Scholar