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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 1/2007

01-01-2007 | Original Paper

Cyclooxygenase-2 Expression in Hepatocellular Carcinoma, Cirrhosis and Chronic Hepatitis in the United States

Authors: Sassan Pazirandeh, Urmila Khettry, Fredric D. Gordon, Robert H. Resnick, Jessica E. Murray, Sunil G. Sheth

Published in: Digestive Diseases and Sciences | Issue 1/2007

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Abstract

Aberrant expression of cyclooxygenase-2 in hepatocellular carcinoma was described in Asia. Using immunohistochemistry, we studied the expression of cyclooxygenase-2 in hepatocellular carcinoma, chronic hepatitis, and cirrhosis in a US institution. A staining score of 0–5 representing the sum of an intensity score and a distribution score was used. The mean scores were 2.2±1.60 for chronic hepatitis, 4.37±1.15 for cirrhosis, and 4.76±0.54 for hepatocellular carcinoma. We found a significant difference in mean staining scores between chronic hepatitis and cirrhosis (p < 0.0001), as well as between chronic hepatitis and hepatocellular carcinoma (p < 0.0001). Fibrosis correlated with cyclooxygenase-2 staining score (r=0.65). In conclusion: (1) Cyclooxygenase-2 expression is higher in cirrhosis and hepatocellular carcinoma when compared to chronic hepatitis. (2) Cyclooxygenase-2 expression correlates with the stage of fibrosis. (3) These results imply that in chronic hepatitis and possibly in cirrhosis, hepatocarcinogenesis may be a cyclooxygenase-2 dependent mechanism.
Literature
1.
El-Serag HB, Mason AC (1999) Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 340:745–750PubMedCrossRef
2.
Benvegnu L, Gios M, Boccato S, Alberti A (2004) Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications. Gut 53:744–749PubMedCrossRef
3.
Bismuth H, Majno PE, Adam R (1999) Liver transplantation for hepatocellular carcinoma. Semin Liver Dis 19:311–322PubMedCrossRef
4.
Llovet JM, Bruix J, Gores GJ (2000) Surgical resection versus transplantation for early hepatocellular carcinoma: clues for the best strategy. Hepatology 31:1019–1021PubMedCrossRef
5.
Mor E, Kaspa RT, Sheiner P, Schwartz M (1998) Treatment of hepatocellular carcinoma associated with cirrhosis in the era of liver transplantation. Ann Intern Med 129:643–653PubMed
6.
Nagasue N, Kohno H, Chang YC, Taniura H, Yamanoi A, Uchida M, Kimoto T, Takemoto Y, Nakamura T, Yukaya H (1993) Liver resection for hepatocellular carcinoma. Results of 229 consecutive patients during 11 years. Ann Surg 217:375–384PubMedCrossRef
7.
Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H, Nakajima Y, Ohnishi K (1985) Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 56:918–928PubMedCrossRef
8.
Sugioka A, Tsuzuki T, Kanai T (1993) Postresection prognosis of patients with hepatocellular carcinoma. Surgery 113:612–618PubMed
9.
Stadlbauer V, Schaffellner S, Kniepeiss D, Jakoby E, Stauber R, Iberer F, Tscheliessnigg KH (2004) Experiences in liver transplantation for hepatocellular carcinoma. Transplant Proc 36:195–198PubMedCrossRef
10.
Radaeva S, Li Y, Hacker HJ, Burger V, Kopp-Schneider A, Bannasch P (2000) Hepadnaviral hepatocarcinogenesis: in situ visualization of viral antigens, cytoplasmic compartmentation, enzymic patterns, and cellular proliferation in preneoplastic hepatocellular lineages in woodchucks. J Hepatol 33:580–600PubMedCrossRef
11.
Huang SN, Chisari FV (1995) Strong, sustained hepatocellular proliferation precedes hepatocarcinogenesis in hepatitis B surface antigen transgenic mice. Hepatology 21:620–626PubMed
12.
Dunsford HA, Sell S, Chisari FV (1990) Hepatocarcinogenesis due to chronic liver cell injury in hepatitis B virus transgenic mice. Cancer Res 50:3400–3407PubMed
13.
Ueno Y, Moriyama M, Uchida T, Arakawa Y (2001) Irregular regeneration of hepatocytes is an important factor in the hepatocarcinogenesis of liver disease. Hepatology 33:357–362PubMedCrossRef
14.
Hu KQ (2002) Rationale and feasibility of chemoprevention of hepatocellular carcinoma by cyclooxygenase-2 inhibitors. J Lab Clin Med 139:234–243PubMedCrossRef
15.
Williams CS, Mann M, DuBois RN (1999) The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 18:7908–7916PubMedCrossRef
16.
DuBois RN, Eberhart CF, Williams CS (1996) Introduction to eicosanoids and the gastroenteric tract. Gastroenterol Clin North Am 25:267–277PubMedCrossRef
17.
Eberhart CE, Dubois RN (1995) Eicosanoids and the gastrointestinal tract. Gastroenterology 109:285–301PubMedCrossRef
18.
Fosslien E (2000) Biochemistry of cyclooxygenase (COX)-2 inhibitors and molecular pathology of COX-2 in neoplasia. Crit Rev Clin Lab Sci 37:431–502PubMedCrossRef
19.
Williams CS, Tsujii M, Reese J, Dey SK, DuBois RN (2000) Host cyclooxygenase-2 modulates carcinoma growth. J Clin Invest 105:1589–1594PubMedCrossRef
20.
Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93:705–716PubMedCrossRef
21.
Masferrer JL, Koki A, Seibert K (1999) COX-2 inhibitors. A new class of antiangiogenic agents. Ann NY Acad Sci 889:84–86PubMedCrossRef
22.
Kondo M, Yamamoto H, Nagano H, Okami J, Ito Y, Shimizu J, Eguchi H, Miyamoto A, Dono K, Umeshita K, Matsuura N, Wakasa K, Nakamori S, Sakon M, Monden M (1999) Increased expression of COX-2 in nontumor liver tissue is associated with shorter disease-free survival in patients with hepatocellular carcinoma. Clin Cancer Res 5:4005–4012PubMed
23.
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 in human hepatocellular carcinoma: relevance to tumor dedifferentiation. Hepatology 29:688–696PubMedCrossRef
24.
Shiota G, Okubo M, Noumi T, Noguchi N, Oyama K, Takano Y, Yashima K, Kishimoto Y, Kawasaki H (1999) Cyclooxygenase-2 expression in hepatocellular carcinoma. Hepatogastroenterology 46:407–412PubMed
25.
Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, Kitamura T, Nakanishi K, Fujimoto I, Inoue A, Yamazaki H et al. (1993) Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 328:1797–1801PubMedCrossRef
26.
Hu KQ, Tong MJ (1999) The long-term outcomes of patients with compensated hepatitis C virus-related cirrhosis and history of parenteral exposure in the United States. Hepatology 29:1311–1316PubMedCrossRef
27.
Batts KP, Ludwig J (1995) Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol 19(12):1409–1417PubMedCrossRef
28.
Sano H, Kawahito Y, Wilder RL, Hashiramoto A, Mukai S, Asai K, Kimura S, Kato H, Kondo M, Hla T (1995) Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Res 55:3785–3789PubMed
29.
Dimberg J, Samuelsson A, Hugander A, Soderkvist P (1999) Differential expression of cyclooxygenase 2 in human colorectal cancer. Gut 45:730–732PubMedCrossRef
30.
Hao X, Bishop AE, Wallace M, Wang H, Willcocks TC, Maclouf J, Polak JM, Knight S, Talbot IC (1999) Early expression of cyclo-oxygenase-2 during sporadic colorectal carcinogenesis. J Pathol 187:295–301PubMedCrossRef
31.
Chapple KS, Cartwright EJ, Hawcroft G, Tisbury A, Bonifer C, Scott N, Windsor AC, Guillou PJ, Markham AF, Coletta PL, Hull MA (2000) Localization of cyclooxygenase-2 in human sporadic colorectal adenomas. Am J Pathol 156:545–553PubMed
32.
Lim HY, Joo HJ, Choi JH, Yi JW, Yang MS, Cho DY, Kim HS, Nam DK, Lee KB, Kim HC (2000) Increased expression of cyclooxygenase-2 protein in human gastric carcinoma. Clin Cancer Res 6:519–525PubMed
33.
Gupta S, Srivastava M, Ahmad N, Bostwick DG, Mukhtar H (2000) Over-expression of cyclooxygenase-2 in human prostate adenocarcinoma. Prostate 42:73–78PubMedCrossRef
34.
Ochiai M, Oguri T, Isobe T, Ishioka S, Yamakido M (1999) Cyclooxygenase-2 (COX-2) mRNA expression levels in normal lung tissues and non-small cell lung cancers. Jpn J Cancer Res 90:1338–1343PubMed
35.
Uefuji K, Ichikura T, Mochizuki H, Shinomiya N (1998) Expression of cyclooxygenase-2 protein in gastric adenocarcinoma. J Surg Oncol 69:168–172PubMedCrossRef
36.
Bae SH, Jung ES, Park YM, Kim BS, Kim BK, Kim DG, Ryu WS (2001) Expression of cyclooxygenase-2 (COX-2) in hepatocellular carcinoma and growth inhibition of hepatoma cell lines by a COX-2 inhibitor, NS-398. Clin Cancer Res 7:1410–1418PubMed
37.
Rahman MA, Dhar DK, 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 7:1325–1332PubMed
38.
Kern MA, Schubert D, Sahi D, Schoneweiss MM, Moll I, Haugg AM, Dienes HP, Breuhahn K, Schirmacher P (2002) Proapoptotic and antiproliferative potential of selective cyclooxygenase-2 inhibitors in human liver tumor cells. Hepatology 36:885–894PubMed
39.
Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364PubMedCrossRef
40.
Yoshiji H, Kuriyama S, Yoshii J, Yamazaki M, Kikukawa M, Tsujinoue H, Nakatani T, Fukui H (1998) Vascular endothelial growth factor tightly regulates in vivo development of murine hepatocellular carcinoma cells. Hepatology 28:1489–1496PubMedCrossRef
41.
Hsu PI, Chow NH, Lai KH, Yang HB, Chan SH, Lin XZ, Cheng JS, Huang JS, Ger LP, Huang SM, Yen MY, Yang YF (1997) Implications of serum basic fibroblast growth factor levels in chronic liver diseases and hepatocellular carcinoma. Anticancer Res 17:2803–2809PubMed
42.
Yamaguchi R, Yano H, Iemura A, Ogasawara S, Haramaki M, Kojiro M (1998) Expression of vascular endothelial growth factor in human hepatocellular carcinoma. Hepatology 28:68–77PubMedCrossRef
43.
Miura H, Miyazaki T, Kuroda M, Oka T, Machinami R, Kodama T, Shibuya M, Makuuchi M, Yazaki Y, Ohnishi S (1997) Increased expression of vascular endothelial growth factor in human hepatocellular carcinoma. J Hepatol 27:854–861PubMedCrossRef
44.
Lai CL, Lau JY, Wu PC, Ngan H, Chung HT, Mitchell SJ, Corbett TJ, Chow AW, Lin HJ (1993) Recombinant interferon-alpha in inoperable hepatocellular carcinoma: a randomized controlled trial. Hepatology 17:389–394PubMedCrossRef
Metadata
Title
Cyclooxygenase-2 Expression in Hepatocellular Carcinoma, Cirrhosis and Chronic Hepatitis in the United States
Authors
Sassan Pazirandeh
Urmila Khettry
Fredric D. Gordon
Robert H. Resnick
Jessica E. Murray
Sunil G. Sheth
Publication date
01-01-2007
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 1/2007
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-006-9184-3

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