Sains Malaysiana 44(5)(2015): 727–733

 

High Expression of Cyclooxygenase-2 in High Grade Human Prostate Adenocarcinoma

(Pengekspresan Tinggi Siklooksigenase-2 dalam Adenokarsinoma Prostat Manusia Gred Tinggi)

 

MOHD ROHAIZAD MD RODUAN1*, NORHAFIZAH MOHTARRUDIN1, CHONG PEI PEI2,

MALINA OSMAN3 & NORAINI MOHD DUSA4

 

1Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia,

43400 Serdang, Selangor Darul Ehsan, Malaysia

 

2Department of Biomedical Sciences, Faculty of Medicine and Health Sciences,

Universiti Putra Malaysia, 43400 Serdang, Selangor Darul Ehsan, Malaysia

 

3Department of Medical Microbiology & Parasitology, Faculty of Medicine and Health Sciences,

Universiti Putra Malaysia, 43400 Serdang, Selangor Darul Ehsan, Malaysia

 

4Department of Pathology, Hospital Kuala Lumpur, Jalan Pahang, 50588 Kuala Lumpur

Malaysia

 

Received: 17 May 2013/Accepted: 22 December 2014

 

ABSTRACT

Inflammation plays an important role to the process of prostate carcinogenesis by increasing the rate of cell proliferation, which contributes to an aggressive tumour phenotype. Cyclooxygenase-2 (COX-2) has been found overexpressed in various types of cancer cells including prostate. The aim of this study was to investigate the COX-2 expressions in different types of human prostate tissues. Paraffin-embedded prostate tissues from 263 samples were examined for the expression of COX-2 marker by immunohistochemistry method. COX-2 was found highly expressed in prostate adenocarcinoma (p=0.001) as compared to benign and normal tissues. The score of COX-2 expressions in most of normal prostate was weak 49 (77.8%), while only 16 (16%) of BPH showed strong expression. 56 cases (56%) prostate cancer showed strong COX-2 expression. Prostate cancer cases showed significant differences in staining patterns as tumour grade increased. In addition, COX-2 expression was significantly correlated with Gleason score in cancerous tissues. This study suggests that COX-2 overexpression is associated with prostate cancer and higher grade tumour.

 

Keywords: Cyclooxygenase-2 (COX-2); immunohistochemistry; inflammations; overexpression; prostate adenocarcinoma

 

ABSTRAK

Inflamasi memainkan peranan penting dalam proses pembentukan kanser prostat melalui peningkatan kadar pembahagian sel. Inflamasi juga bertanggungjawab dalam pembentukan fenotip kanser prostat yang lebih agresif. Siklooksigenase-2 (COX-2 didapati diekspres lebih tinggi daripada aras biasa dalam pelbagai jenis sel kanser termasuk prostat. Tujuan kajian ini dijalankan adalah untuk mengkaji pengekspresan COX-2 dalam tisu prostat manusia yang berbeza. Sebanyak 263 tisu prostat tertanam parafin telah digunakan untuk mengkaji aras pengekspresan penanda COX-2 melalui kaedah imunohistokimia. Pengekspresan COX-2 didapati lebih tinggi dalam tisu adenokarsinoma prostat (p=0.001) berbanding tisu benigna dan tisu prostat yang normal. Kebanyakan tisu prostat normal mengekspres COX-2 yang lemah 49 (77.8%) dan hanya 16 (16%) tisu BPH menunjukkan pengekspresan COX-2 yang kuat. Manakala, 56 (56%) tisu kanser prostat menunjukkan pengekspresan COX-2 yang kuat. Tisu kanser prostat juga menunjukkan perbezaan corak perwarnaan COX-2 yang signifikan dengan peningkatan gred tumor. Selain itu, pengekspresan COX-2 menunjukkan perhubungan yang signifikan dengan skor Gleason dalam tisu kanser. Kajian ini mencadangkan bahawa terdapat hubungan antara pengekspresan COX-2 yang sangat tinggi dengan kanser prostat dan tumor gred tinggi.

 

Kata kunci: Adenikarsinoma prostat; siklooksigenase-2 (COX-2); imunohistokimia; inflamasi; pengekspresan

REFERENCES

Bosland, M.C., Oakley-Girvan, I. & Whittemore, A.S. 1999. Dietary fat, calories and prostate cancer risk. J. Natl. Cancer Inst. 91: 489-491.

Chan, G., Boyle, J.O., Yang, E.K., Zhang, F., Sacks, P.G., Shah, J.P., Edelstein, D., Soslow, R.A., Koki, A.T., Woerner, B.M., Masferrer, J.L. & Dannenberg, A.J. 1999. Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck. Cancer Res. 59: 991-994.

Chapple, K.S., Scott, N., Guillou, P.J., Coletta, P.L. & Hull, M.A. 2002. Interstitial cell cyclooxygenase-2 expression is associated with increased angiogenesis in human sporadic colorectal adenomas. J. Pathol. 198: 435-441.

Chu, J., Llyod, F.L., Trifan, O.C., Knapp, B. & Rizzo, M.T. 2003. Potential involvement of cyclooxygenase-2 pathway in the regulation of tumour associated angiogenesis and growth in pancreatic cancer. Mol. Cancer Ther. 2: 1-7.

Coussens, L.M. & Werb, Z. 2001. Inflammatory cells and cancer: Think different! J. Exp. Med. 193: F 23- 26.

Davies, G., Salter, J., Hills, M., Martin, L.A., Sacks, N. & Dowsett, M. 2003. Correlation between cyclooxygenase-2 expression and angiogenesis in human breast cancer. Clin. Cancer Res. 9: 2651-2656.

Fujiwaki, R., Iida, K., Kanasaki, H., Ozaki, T., Hata, K. & Miyazaki, K. 2002. Cyclooxygenase-2 expression in endometrial cancer: Correlation with microvessel count and expression of vascular endothelial growth factor and thymidine phosphorylase. Hum. Pathol. 33: 213-219.

Gottard, S. 1986. Relevance of fatty acids and eicosanoids to clinical and preventive medicine. Prog. Lipid Res. 25: 1-4.

Gupta, S., Srivastava, M., Ahmad, N., Bostwick, D.G. & Mukhtar, H. 2000. Over-expression of cyclooxygenase-2 in human prostate adenocarcinoma. Prostate 42: 73-78.

Hao, Y., Gu, X., Zhao, Y., Stephen, G., Sha, W., Duane, T., Smoot, J.C., Wu, T.C. & Xiaowu, P. 2011. Enforced expression of miR-101 inhibits prostate cancer cell growth by modulating the COX-2 pathway in vivo. Cancer Prev. Res. 4(7): 1073- 1083.

Herschman, H.R. 1991. Primary response genes induced by growth factors and tumor promoters. Annu. Rev. Biochem. 60: 281-319.

Hla, T.A., Ristimaki & Sano, H. 1999. Role of the early gene Cyclooxygenase-2 (COX-2) in angiogenesis. Cancer Res. 59: 2223-2228.

Hwang, D., Scollard, D., Byrne, J. & Levine, E. 1998. Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. J. Natl. Cancer Inst. 90: 455-460.

Kakiuchi, Y., Tsujii, S., Tsujii, M., Murata, H., Kawai, N., Yasumaru, M., Kimura, A., Komori, M., Irie, T., Miyoshi, E., Sasaki, Y., Hayashi, N., Kawano, S. & Hori, M. 2002. Cyclooxygenase-2 activity altered the cell-surface carbohydrate antigens on colon cancer cells and enhanced liver metastasis. Cancer Res. 62: 1567-1572.

Kazuhiko, U., Ichikura, T., Mochizuki, H. & Shinomiya, N. 1998. Expression of cyclooxygenase-2 protein in gastric adenocarcinoma. J. Surg. Oncol. 69: 168-172.

Koga, H., Sakisaka, S., Ohishi, M., Kawaguchi, T., Taniguchi, E., Sasatomi, K., Harada, M., Kusaba, T., Tanaka, M., Kimura, R., Nakashima, Y., Nakashima, O., Kojiro, M., Kurohiji, T. & Sata, M. 1999. Expression of cyclooxygenase-2 human hepatocellular carcinoma: Relevance to tumor dedifferentiation. Hepatology 29: 688-696.

Leung, W.K., To, K.F., Go, M.Y., Chan, K.K., Chan, F.K., Ng, E.K., Chung, S.C. & Sung, J.J. 2003. Cox-2 up-regulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma. Int. J. Oncol. 23: 1317-1322.

Liu, X.H., Kirschenbaum, A., Yao, S. & Levine, A.C. 1998. NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis and down-regulates bcl-2 expression in LNCaP cells. Cancer Res. 58: 4245-4249.

Liu, X.H., Kirschenbaum, A., Yao, S., Lee, R., Holland, J.F. & Levine, A.C. 2000. Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate cancer in vivo. J. Urol. 164: 820-825.

Madaan, S., Abel, P.D., Hewitt, R., Chaudhary, K.S., Stott, M.A., Stamp, G.W.H. & Lalani, E.N. 2000. Cytoplasmic induction and overexpression of cyclooxygenase-2 in human prostate cancer: Implications for prevention and treatment. Br. J. Urol. 86: 736-741.

Mostafa, M.K., Samira, A.M., Samia, M.G. & Moustafa, A.A.S. 2009. Cyclooxygenas-2 (COX-2) expression in Egyptian case of benign prostatic hyperplasia and prostatic adenocarcinoma. Acad. J. of Cancer Research 2: 33-39.

National Cancer Registry. 3rd ed. Ministry of Health, Malaysia. 2008. Cancer Incidence in Peninsular Malaysia 2003 – 2005. Kuala Lumpur: National Printers Malaysia.

O'Neill, G.P. & Ford-Hutchinson, A.W. 1993. Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBBS Lett. 330: 156-160.

Oshima, M., Dinchuk, J.E., Kargman, S.L., Oshima, H., Hancock, B., Kwong, E., Trzaskos, J.M., Evans, J.F. & Taketo, M.M. 1996. Supression of intestinal polyposis in Apc?716 knockout mice by inhibition of Cyclooxgenase-2 (COX-2). Cell 87: 803-809.

Rahman, M., Selvarajan, K., Hasan, M.R., Chan, A.P., Jiri, C., Kim, J., Chen, S.K., Le, N.D., Kim, Y.B. & Tai, I.T. 2012. Inhibition of COX-2 in colon cancer modulates tumour growth and MDR-1 expression to enhance tumour regression in therapy-refractory cancers in vivo. Neoplasia 14(7): 624- 633.

Rahman, M.A., Dhar, D.K., Yamaguchi, E., Maruyama, S., Sato, T., Hayashi, H., Ono, T., Yamanoi, A., Kohno, H. & Nagasue, N. 2001. Coexpression of inducible nitric oxide synthase and COX-2 in hepatocellular carcinoma and surrounding liver: Possible involvement of COX-2 in the angiogenesis of hepatitis C virus-positive cases. Clin. Cancer Res. 7(5): 1325-1332.

Rodney, T.M. 2005. Immunohistochemical markers of prostate carcinoma, including prostate-specific membrane antigen (PSMA). ProPath. Sep 13: 1-2.

Shappell, S., Manning, S., Boeglin, W., Guan, Y., Roberts, R., Davis, L., Olson, S., Jack, G., Coeffy, C., Wheeler, T., Breyer, M. & Brash, A. 2001. Alteration in lipooxygenase and cyclooxygenase catalytic anctivity and mRNA expression in prostate carcinoma. Neoplasia 3: 287-303.

Sheng, H.J., Shao, M., Washington, M.K. & DubBois, R.N. 2001. Prostaglandin E2 increases growth and motility of colorectal carcinoma cells. J. Biol. Chem. 276: 18075-18081.

Song, X.Q., Lin, H.P., Johnson, A.J., Tseng, P.H., Yang, Y.T., Kulp, S.K. & Chen, C.S. 2002. Cyclooxygenase-2 player or spectator in cyclooxygenase-2 inhibitor-induced apoptosis in prostate cancer cells. J. Natl. Cancer Inst. 94: 585-591.

Tsujii, M. & DuBois, R.N. 1995. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase-2. Cell 83: 450-493.

Tsujii, M., Kawano, S., Tsuji, S., Sawaoka, H., Hori, M. & DuBois, R.N. 1998. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93: 705-716.

Varma, M. & Jasani, B. 2005. Diagnostic utility of immunohistochemistry in morphologically difficult prostate cancer. Histopathology 47: 1-16.
Wang, W., Bergh, A. & Damber, J.E. 2005. Cyclooxygenase-2 expression correlates with local chronic inflammation and tumor neovascularization in human prostate cancer. Clin. Cancer Res. 11: 3250-3256.

Weitzman, S.A. & Gordon, L.I. 1993. Inflammation and cancer: Role of phagocyte-generated oxidants in carcinogenesis. Blood 76: 655-663.
Wolff, H., Saukkonen, K., Anttila, S., Karjalainen, A., Vainio, H. & Ristimaki, A. 1998. Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res. 58: 4997-5001.

Yoshimura, R., Sano, H., Masuda, C., Kawamura, M., Tsubouchi, Y., Chargui, J., Yoshimura, N., Hla, T. & Wada, S. 2000. Expression of cyclooxygenase-2in prostate carcinoma. Cancer 89: 589-596.

Zha, S., Gage, W., Sauvageot, J., Elizabeth, A., Mathew, J., Charles, M., Dennis, A., William, G., Angelo, M. & Charles, M. 2001. Cyclooxygenase-2 is up-regulated in proliferative inflammatory atrophy of the prostate, but not in prostatic carcinoma. Cancer Res. 61: 8617-8623.

Zimmermann, K.C., Sarbia, M., Weber, A.A., Borchard, F., Gabbert, H.E. & Schrör, K. 1999. Cyclooxygenase-2 expression in human esophageal carcinoma. Cancer Res. 59: 198-204.

 

*Corresponding author; email: ijad_27@yahoo.com