EVALUATION OF COX2 EXPRESSION AS A PROGNOSTIC MARKER IN COLORECTAL ADENO CARCINOMA
Abstract
Introduction: Colon adenocarcinoma (COAD), the fourth most common malignant cancer, has been the fifth leading cause of cancer-related death diseases worldwide. It was estimated that nearly 101,420 new COAD cases were diagnosed and 27,640 deaths in the United States in 2019. COX2 has an important role in colorectal tumorigenesis and the strong relationship between COX2/prostaglandin E2 (PGE2) signaling pathway and adenomatous polyposis coli gene (APC) expression in intestinal neoplasia and also plays an important role in carcinogenesis, suppression of apoptosis, angiogenesis, and metastasis of colon cancer.
Aim of the work: To evaluate COX2 expression in sporadic cases of colorectal adenocarcinoma in Tobruk-Libya
Patients, Materials, and Methods: The study group included 60 selected cases of colorectal adenocarcinoma, diagnosed at the Pathology department of Tobruk Medical Center, Libya, between 2016 and 2019. All patients were surgically treated and underwent right or left hemicolectomy according to the site of the tumor.
Results: The details of 60 patients selected for analyses are as follows. The mean age of the patients at initial surgery was 48.3 years (range, 38–72 years), and 42 were (70%) males and 18 (30%) were females. 18 cases of the tumors were well-differentiated adenocarcinoma (30%); 36 cases were moderately differentiated adenocarcinoma (60%) and 6 cases were poorly differentiated adenocarcinoma (10%).
Conclusion: COX2 could be used as useful markers to detect the invasiveness of colorectal adenocarcinoma. Aspirin can be used for the prevention of colorectal adenocarcinoma.
Keywords:
Immunohistochemistry (IHC), COX2, Colorectal adenocarcinoma
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References
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Zhi-Yin H, Lin-Hao Z, Chong Z, Rui L, Huan T, Can G, Tian L, Cheng-Wei T, Jin-Hang G. High HIF-1α expression predicts poor prognosis of patients with colon adenocarcinoma. Int J Clin Exp Pathol 2018;11(12):5635-5646.
Cossiolo DC, Costa HCM, Fernandes KBP, Laranjeira LLS, Fernandes MTP, Poli-Frederico RC. Polymorphism of the cox-2 gene and susceptibility to colon and rectal cancer. ABCD Arq Bras Cir Dig 2017;30(2):114-117.
Karin M, Cao Y, Greten FR, Li Z-W. NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer. 2002;2(4):301–10.
Akkiz H, Bayram S, Bekar A, Akgollu E, Ulger Y. Functional polymorphisms of cyclooxygenase-2 gene and risk for hepatocellular carcinoma. Mol Cel Biochem. 2011;347(1-2): 201-8.
Wallace JL, Devchand PR. Emerging roles for cyclooxygenase-2 in gastrointestinal mucosal defense. Br J Pharmacol. 2005;145(3):275–82.
Murdani A, Aziz R, Aru WS, Dadang M, Diah RH, Bethy SH. Expression of NF-kB and COX2 in Colorectal Cancer among Native Indonesians: The Role of Inflammation in Colorectal Carcinogenesis. Indones J Intern Med. 2013;45(3):187-92
Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE: Cyclooxygenase in biology and disease. FASEB J 1998;12:1063-1073.
Williams CS, Mann M, DuBois RN: The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 1999;18:7908-7916.
Sano H, Kawahito Y, Wilder RL, Hashiramoto A, Mukai S, Asai K, Kimura S, Kato H, Kondo M, Hla T: Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Res 1995;55:3785–3789.
Kargman SL, O’Neill GP, Vickers PJ, Evans JF, Mancini JA, Jothy S: Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Res 1995;55:2556-2559.
Reddy BS, Hirose Y, Lubet R, Steele V, Kelloff G, Paulson S, Seibert K, Rao CV: Chemoprevention of colon cancer by specific cyclooxygenase-2 inhibitor, celecoxib, administered during different stages of carcinogenesis. Cancer Res 2000;60:293-297.
Kawamori T, Rao CV, Seibert K, Reddy BS: Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res 1998;58:409-412.
Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su LK, Levin B: The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000;342:1946-1952.
Sheng H, Shao J, Kirkland SC, Isakson P, Coffey RJ, Morrow J, Beauchamp RD, DuBois RN: Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. J Clin Invest 1997;99:2254-2259.
Renkonen J, Wolff H and Paavonen T: Expression of cyclooxygenase-2 in human tongue carcinoma and its precursor lesions. Virchows Arch; 2002;440(6):594-597.
Kuroda J, Urade M, Kishimoto H, Noguchi K, Hashitani S, Sakurai K, Nishimura N, Hashimoto-Tamaoki T: Promotion of cell differentiation, and suppression of cell growth and cyclooxygenase2 expression by differentiation-inducing agents in human oral squamous carcinoma SCC 25 cells. Int J Oncol 2005;3:361–367.
Segawa E, Sakurai K, Kishimoto H, et al.: Expression of cyclooxygenase-2 and DNA topoisomerase II α in precancerous and cancerous lesions of the oral mucosa. Oral Oncology 2008;44:664– 671.
Shibata M, Kodani I, Osaki M, et al.: Cyclooxygenase-1and-2 expression in human oral mucosa, dysplasias and squamous cell carcinomas and their pathological significance. Oral Oncol 2005;41(3):304–312.
Sakurai A, Masahiro U, Kazuma N, et al.: Prognostic significance of cyclooxygenase 2 and DNA topoisomeraseII α expression in oral carcinoma. 2006;DOI: 10.1002/hed.
Augusto J, Cassiano F, Márcia C et al.: Immunoexpression of cyclooxygenase-2 and p53 in oral squamous cell carcinoma. American Journal of Otolaryngology 2009;30:89–94.
Tan K and Putti T: Cyclooxygenase-2 expression in nasopharyngeal carcinoma: immunohistochemical findings and potential implications. J Clin Pathol 2005;58:535–538.
Ratnasinghe D, Tangrea J, Roth M, et al.: Expression of cyclooxygenase-2 in human squamous cell carcinoma of the esophagus; an immunohistochemical survey. Anti cancer Res 1999;19:171–174.
Kawata R, Sawako H, Michitoshi A et al.: Expression of cyclooxygenase-2 and microsomal prostagalandin E synthase-1 in head and neck squamous cell carcinoma. Auris Nasus Larynx 2010;379:482–487.
Itoh S, Kazuhiro M, Isao F et al.: Immunohistochemical study on over expression of cyclooxygenase-2 in squamous cell carcinoma of the oral cavity: its importance as a prognostic predictor. Oral Oncology 2003;39: 829–835.
Pannone G, Bufo P, Serpico K, et al.: Cyclooxygenase-2 expression in Oral squamous cell carcinoma. Int J Immunopathol-Pharmacol 2004;3:273-82.
Lee D, Park S, Park S, et al.: Effects of p53 or p27 on cycloxygenase-2 gene expression in head and neck squamous cell carcinoma cell lines. Head Neck 2004;26(8):706-715.
Choi E, Heo J, Oh J, et al.: COX-2 regulates p53 activity and inhibits DNA damage induced apoptosis. Biochem Biophys Res Comm 2005;328 (4):1107-1112.
Corcoran C, He K, Huang Y, et al.: Cyclooxygenase interacts with p53 and interferes with p53-dependent transcription and apoptosis. Oncogene 2005;24(9):1634-1640.
Jackel E, Raja S, Tan J, et al.: Correlation of expression of cyclooxygenase-2, vascular endothelial growth factor, peroxisome proliferator-activated receptor (delta) with head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2001;127: 1253-1259.
Kyzas P, Dimitrios S and Niki J: COX-2 expression correlates with VEGF-C and lymph node metastases in patients with head and neck squamous cell carcinoma. Modern Pathology 2005;18:153–160.
Kraisorn S, Yaowapa M, Somporn S, et al.: Expression of proinfammatory protein, iNOS, VEGF and COX-2 in Oral Squamous Cell Carcinoma (OSCC), relationship with angiogenesis and their clinicopathological correlation. Med Oral Patol Oral Cir Bucal 2009;14 (7):319-324.
Seno H, Oshima M, Ishikawa T, et al.: Cyclooxygenase2-and prostaglandin E (2) receptor EP (2) dependent angiogenesis in Apc (Delta716) mouse intestinal polyps. Cancer Res 2002;62:506–511.
Cohen E, Almahmeed T, Du B, et al.: Microsomal prostaglandin E synthase-1 is over expressed in head and neck squamous cell carcinoma. Clin Cancer Res 2003;9:3425–3430.
Castellone M, Teramoto H, Williams B, et al.: Prostaglandin E2 promotes colon cancer cell growth through a Gsaxin-beta-catenin signaling axis. Sience 2005;310:1504–1510.
Von Rahden B, Stein H, Puhringer F, et al.: Coexpression of cyclooxygenases (COX-1, COX-2) and vascular endothelial growth factors (VEGF-A,VEGF-C) in esophageal adenocarcinoma. Cancer Res 2005;65(12): 5038-5044.
Toomey D, Murphy L and Conlon K: COX-2, VEGF and tumor angiogenesis. Surgeon 2009:174-180.
Gallo O, Alessandro F, Lucia M, et al.: Cyclooxgenase 2 pathway correlates with VEGF expression in head and neck cancer. Implication for tumor angiogenesis and metastasis. Neoplasia 2001;3(1):53- 61.
Ogata S, Kubota Y, Yamashiro T, et al.: Signaling pathways regulating IL-1alpha-induced COX-2 expression. J Dent Res 2007;86:186–191.
Eberhart C, Coffey R, Radhika A, et al.: Up-regulation of cyclooxygenase2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994;107(4):1183–1188.
Hida T, Yatabe Y, Achiwa H, et al.: Increased expression of cyclooxygenase-2 occurs frequently in human lung cancer, specifically in adenocarcinomas. Cancer Res 1998;58(17):3761–3764.
Nozoe T, Ezaki T, Kabashima A, et al.: Significance of immunohistochemical expression of cyclooxygenase-2 in squamous cell carcinoma of the esophagus. Am J Surg 2005;189(1):110–115.
Takatori H, Natsugoe S, Okumura H, et al.: Cyclooxygenase-2 expression is related to prognosis in patients with esophageal squamous cell carcinoma. EJSO 2008;34:397-402.
Zhi-Yin H, Lin-Hao Z, Chong Z, Rui L, Huan T, Can G, Tian L, Cheng-Wei T, Jin-Hang G. High HIF-1α expression predicts poor prognosis of patients with colon adenocarcinoma. Int J Clin Exp Pathol 2018;11(12):5635-5646.
Cossiolo DC, Costa HCM, Fernandes KBP, Laranjeira LLS, Fernandes MTP, Poli-Frederico RC. Polymorphism of the cox-2 gene and susceptibility to colon and rectal cancer. ABCD Arq Bras Cir Dig 2017;30(2):114-117.
Karin M, Cao Y, Greten FR, Li Z-W. NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer. 2002;2(4):301–10.
Akkiz H, Bayram S, Bekar A, Akgollu E, Ulger Y. Functional polymorphisms of cyclooxygenase-2 gene and risk for hepatocellular carcinoma. Mol Cel Biochem. 2011;347(1-2): 201-8.
Wallace JL, Devchand PR. Emerging roles for cyclooxygenase-2 in gastrointestinal mucosal defense. Br J Pharmacol. 2005;145(3):275–82.
Murdani A, Aziz R, Aru WS, Dadang M, Diah RH, Bethy SH. Expression of NF-kB and COX2 in Colorectal Cancer among Native Indonesians: The Role of Inflammation in Colorectal Carcinogenesis. Indones J Intern Med. 2013;45(3):187-92
Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE: Cyclooxygenase in biology and disease. FASEB J 1998;12:1063-1073.
Williams CS, Mann M, DuBois RN: The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 1999;18:7908-7916.
Sano H, Kawahito Y, Wilder RL, Hashiramoto A, Mukai S, Asai K, Kimura S, Kato H, Kondo M, Hla T: Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Res 1995;55:3785–3789.
Kargman SL, O’Neill GP, Vickers PJ, Evans JF, Mancini JA, Jothy S: Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Res 1995;55:2556-2559.
Reddy BS, Hirose Y, Lubet R, Steele V, Kelloff G, Paulson S, Seibert K, Rao CV: Chemoprevention of colon cancer by specific cyclooxygenase-2 inhibitor, celecoxib, administered during different stages of carcinogenesis. Cancer Res 2000;60:293-297.
Kawamori T, Rao CV, Seibert K, Reddy BS: Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res 1998;58:409-412.
Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su LK, Levin B: The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000;342:1946-1952.
Sheng H, Shao J, Kirkland SC, Isakson P, Coffey RJ, Morrow J, Beauchamp RD, DuBois RN: Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. J Clin Invest 1997;99:2254-2259.
Renkonen J, Wolff H and Paavonen T: Expression of cyclooxygenase-2 in human tongue carcinoma and its precursor lesions. Virchows Arch; 2002;440(6):594-597.
Kuroda J, Urade M, Kishimoto H, Noguchi K, Hashitani S, Sakurai K, Nishimura N, Hashimoto-Tamaoki T: Promotion of cell differentiation, and suppression of cell growth and cyclooxygenase2 expression by differentiation-inducing agents in human oral squamous carcinoma SCC 25 cells. Int J Oncol 2005;3:361–367.
Segawa E, Sakurai K, Kishimoto H, et al.: Expression of cyclooxygenase-2 and DNA topoisomerase II α in precancerous and cancerous lesions of the oral mucosa. Oral Oncology 2008;44:664– 671.
Shibata M, Kodani I, Osaki M, et al.: Cyclooxygenase-1and-2 expression in human oral mucosa, dysplasias and squamous cell carcinomas and their pathological significance. Oral Oncol 2005;41(3):304–312.
Sakurai A, Masahiro U, Kazuma N, et al.: Prognostic significance of cyclooxygenase 2 and DNA topoisomeraseII α expression in oral carcinoma. 2006;DOI: 10.1002/hed.
Augusto J, Cassiano F, Márcia C et al.: Immunoexpression of cyclooxygenase-2 and p53 in oral squamous cell carcinoma. American Journal of Otolaryngology 2009;30:89–94.
Tan K and Putti T: Cyclooxygenase-2 expression in nasopharyngeal carcinoma: immunohistochemical findings and potential implications. J Clin Pathol 2005;58:535–538.
Ratnasinghe D, Tangrea J, Roth M, et al.: Expression of cyclooxygenase-2 in human squamous cell carcinoma of the esophagus; an immunohistochemical survey. Anti cancer Res 1999;19:171–174.
Kawata R, Sawako H, Michitoshi A et al.: Expression of cyclooxygenase-2 and microsomal prostagalandin E synthase-1 in head and neck squamous cell carcinoma. Auris Nasus Larynx 2010;379:482–487.
Itoh S, Kazuhiro M, Isao F et al.: Immunohistochemical study on over expression of cyclooxygenase-2 in squamous cell carcinoma of the oral cavity: its importance as a prognostic predictor. Oral Oncology 2003;39: 829–835.
Pannone G, Bufo P, Serpico K, et al.: Cyclooxygenase-2 expression in Oral squamous cell carcinoma. Int J Immunopathol-Pharmacol 2004;3:273-82.
Lee D, Park S, Park S, et al.: Effects of p53 or p27 on cycloxygenase-2 gene expression in head and neck squamous cell carcinoma cell lines. Head Neck 2004;26(8):706-715.
Choi E, Heo J, Oh J, et al.: COX-2 regulates p53 activity and inhibits DNA damage induced apoptosis. Biochem Biophys Res Comm 2005;328 (4):1107-1112.
Corcoran C, He K, Huang Y, et al.: Cyclooxygenase interacts with p53 and interferes with p53-dependent transcription and apoptosis. Oncogene 2005;24(9):1634-1640.
Jackel E, Raja S, Tan J, et al.: Correlation of expression of cyclooxygenase-2, vascular endothelial growth factor, peroxisome proliferator-activated receptor (delta) with head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2001;127: 1253-1259.
Kyzas P, Dimitrios S and Niki J: COX-2 expression correlates with VEGF-C and lymph node metastases in patients with head and neck squamous cell carcinoma. Modern Pathology 2005;18:153–160.
Kraisorn S, Yaowapa M, Somporn S, et al.: Expression of proinfammatory protein, iNOS, VEGF and COX-2 in Oral Squamous Cell Carcinoma (OSCC), relationship with angiogenesis and their clinicopathological correlation. Med Oral Patol Oral Cir Bucal 2009;14 (7):319-324.
Seno H, Oshima M, Ishikawa T, et al.: Cyclooxygenase2-and prostaglandin E (2) receptor EP (2) dependent angiogenesis in Apc (Delta716) mouse intestinal polyps. Cancer Res 2002;62:506–511.
Cohen E, Almahmeed T, Du B, et al.: Microsomal prostaglandin E synthase-1 is over expressed in head and neck squamous cell carcinoma. Clin Cancer Res 2003;9:3425–3430.
Castellone M, Teramoto H, Williams B, et al.: Prostaglandin E2 promotes colon cancer cell growth through a Gsaxin-beta-catenin signaling axis. Sience 2005;310:1504–1510.
Von Rahden B, Stein H, Puhringer F, et al.: Coexpression of cyclooxygenases (COX-1, COX-2) and vascular endothelial growth factors (VEGF-A,VEGF-C) in esophageal adenocarcinoma. Cancer Res 2005;65(12): 5038-5044.
Toomey D, Murphy L and Conlon K: COX-2, VEGF and tumor angiogenesis. Surgeon 2009:174-180.
Gallo O, Alessandro F, Lucia M, et al.: Cyclooxgenase 2 pathway correlates with VEGF expression in head and neck cancer. Implication for tumor angiogenesis and metastasis. Neoplasia 2001;3(1):53- 61.
Ogata S, Kubota Y, Yamashiro T, et al.: Signaling pathways regulating IL-1alpha-induced COX-2 expression. J Dent Res 2007;86:186–191.
Eberhart C, Coffey R, Radhika A, et al.: Up-regulation of cyclooxygenase2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994;107(4):1183–1188.
Hida T, Yatabe Y, Achiwa H, et al.: Increased expression of cyclooxygenase-2 occurs frequently in human lung cancer, specifically in adenocarcinomas. Cancer Res 1998;58(17):3761–3764.
Nozoe T, Ezaki T, Kabashima A, et al.: Significance of immunohistochemical expression of cyclooxygenase-2 in squamous cell carcinoma of the esophagus. Am J Surg 2005;189(1):110–115.
Takatori H, Natsugoe S, Okumura H, et al.: Cyclooxygenase-2 expression is related to prognosis in patients with esophageal squamous cell carcinoma. EJSO 2008;34:397-402.
Published
30/06/2020
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Elsayed, A. G., F. A. Aljali, F. A. Asnini, and A. M. Mohamed. “EVALUATION OF COX2 EXPRESSION AS A PROGNOSTIC MARKER IN COLORECTAL ADENO CARCINOMA”. International Journal of Health Care and Biological Sciences, Vol. 1, no. 1, June 2020, pp. 19-26, https://saapjournals.org/index.php/ijhcbs/article/view/14.
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