Year 2019 / Volume 111 / Number 5
Original
Altered expression of COX-2 and TNF-α in patients with hepatocellular carcinoma

364-370

DOI: 10.17235/reed.2019.5898/2018

Andressa de Freitas Alves, Vanessa Dido Baldissera, Eduardo Cremonese Filippi Chiela, Carlos Thadeu Schmidt Cerski, Paulo Roberto Ott Fontes, Marilda da Cruz Fernandes, Marilene Porawski, Márcia Giovenardi,

Abstract
Background and aim: hepatocellular carcinoma is a type of cancer related with inflammation, as 90% of cases develop in a chronic inflammation condition. Excess inflammation can affect tissue homeostasis. Cytokines and inflammatory mediators are immunological components that can influence the functioning of cells and tissues. In addition, the estrogen receptor appears to play an important role in hepatocarcinogenesis. The aim of the study was to evaluate the expression of inflammatory markers and ER in patients with hepatocellular carcinoma. Methods: data from 143 patients of ISCMPA were analyzed. Immunohistochemistry was performed of cyclooxygenase-2 enzyme (COX-2), nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α) and ER in paraffin-embedded hepatic tissue. The percentage of the stained area, intensity of staining and of the number of ER positive nuclei were evaluated using the ImageJ 1.50 software. Results and conclusion: there was a significant difference between the groups in terms of the percentage of marked area (p = 0.040) for COX-2 and the intensity of staining of TNF-α (p = 0.030). No significant differences were observed in any of other parameters evaluated. In conclusion, COX-2 and TNF-α are possible markers that should be further studied to determine their immunohistochemical profile and role in HCC development.
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References
1. Mcglynn KA, Petrick JL, London WT. Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability. Clin Liver Dis. 2015; 19 (2): 223-38.
2. Forner A, Reig M, Bruix J. Hepatocelullar carcinoma. Lancet. 2018; 391: 1301–14.
3. INCA – Ministério da Saúde. Dados de Incidência de Câncer no Brasil – Estimativa 2018. [Internet] 2018. Available from: http://www.inca.gov.br/estimativa/2018/estimativa-2018.pdf
4. Díaz-González A, Forner A, Rodríguez-de-Lope C, et al. New challenges in clinical research on hepatocellular carcinoma. Rev Esp Enferm Dig. 2016;108(8):485-493.
5. Maiorov EG, Keskin O, Gursoy A, et al. The structural network of inflammation and cancer: Merits and challenges. Semin Cancer Biol. 2013; 23(4): 243-251.
6. Budhu A, Wang XW. The role of cytokines in hepatocellular carcinoma. J Leukoc Biol. 2006; 80(6): 1197-213.
7. Fernandes JV, Cobucci RN, Jatobá CAN, et al. The role of the mediators of inflammation in cancer development. Pathol Oncol Res. 2015; 21(3): 527-34.
8. Capece D, Fischietti M, Verzella D, et al. The inflammatory microenvironment in hepatocellular carcinoma: a pivotal role for tumor-associated macrophages. Biomed Res Int. 2013; 2013:187204.
9. Abbas AK, Lichtman AH. Imunologia básica: funções e distúrbios do sistema imunológico. 3th ed. Rio de Janeiro: Elsevier; 2009. p. 273-8.
10. Thompson PA, Khatami M, Baglole CJ, et al. Environmental immune disruptors, inflammation and cancer risk. Carcinogenesis. 2015; 36 Suppl 1: S232-53.
11. Turculeanu A, Mongoanta CA, Ionita E, et al. TNF-α evaluation in tonsil cancer. Rom J Morphol Embryol. 2015; 56(1): 101-6.
12. Al obeed OA, Alkhayal KA, Al Sheikh A, et al. Increased expression of tumor necrosis factor-α is associated with advanced colorectal cancer stages. World J Gastroenterol. 2014; 20(48): 18390-6.
13. Hammam O, Mahmoud O, Zahran M, et al. A possible role for TNF-α in coordinating inflammation and angiogenesis in chronic liver disease and hepatocellular carcinoma. Gastrointest Cancer Res. 2013; 6(4): 107-114.
14. Szabo G, Lippai D. Molecular hepatic carcinogenesis: Impact of inflammation. Dig Dis. 2012; 30: 243-8
15. Gosh N, Chaki R, Mandal V, et al. COX-2 as a target for cancer chemotherapy. Pharmacol Rep. 2010; 62(2):233-44.
16. Cheng J, Fan X-M. Role of cyclooxygenase-2 in gastric cancer development and progression. World J Gastroenterol. 2013; 19(42): 7361-7368.
17. Cruzs SM, Balkwill FR. Inflammation and cancer: advances and new agents. Nat Rev Clin Oncol. 2015; 12(10):584-96.
18. Chen J, Wu F, Pei H-L, et al. Analysis of the correlation between P53 and Cox-2 expression and prognosis in esophageal cancer. Oncol Lett. 2015; 10(4): v2197-203.
19. Giannitrapani L, Ingrao S, Soresi M, et al. Cyclooxygenase-2 expression in chronic liver diseases and hepatocellular carcinoma. Ann N Y Acad Sci. 2009; 1155: 293-9.
20. Cheng AS-L, Chan HL-Y, Leung WK, et al. Expression of HBx and COX-2 in chronic hepatitis B, cirrhosis and hepatocellular carcinoma: implication of HBx in up-regulation of COX-2. Modern Pathology. 2004; 17: 1169-79.
21. Bae SH, Jung ES, Park YM, et al. Expression of cyclooxygenase-2 (COX-2) in hepatocellular carcinoma and growth inhibition of hepatoma cell lines by a COX-2 inhibitor, NS-3981. Clin Cancer Res. 2001; 7(5):1410-8.
22. Koga H, Sakisaka S, Ohishi M, et al. Expression of cyclooxygenase-2 in human hepatocellular carcinoma: Relevance to tumor dedifferentiation. Hepatology. 1999; 29(3):688-96.
23. Kalra, M, Mayes J, Assefa S, et al. Role of sex steroid receptors in pathobiology of hepatocellular carcinoma. World J Gastroenterol. 2008; 14(39): 5945-61.
24. Zhai Y, Zhou G, Deng G, et al. Estrogen receptor alpha polymorphisms associated with susceptibility to hepatocellular carcinoma in hepatitis B virus carriers. Gastroenterology. 2006; 130: 2001-9.
25. Shi L, Feng Y, Lin H, et al. Role of estrogen in hepatocellular carcinoma: is inflammation the key? J. transl. med. 2014; 12: 1-9.
26. Baumgarten SC, Frasor J. Mini-review: Inflammation: An instigator of more aggressive estrogen receptor (ER)-positive breast cancers. Mol. endocrinol. 2012; 26(3): 360-371.
27. Kwon SH, Jeong SW, Jang JY, et al. Cyclooxygenase-2 and vascular endothelial growth factor in chronic hepatitis, cirrhosis and hepatocellular carcinoma. Clin Mol Hepatol. 2012; 18(3):287-94.
28. Yang Y, Zhu J, Gou H, et al. Clinical significance of Cox-2, Survivin and Bcl-2 expression in hepatocellular carcinoma (HCC). Med Oncol. 2011; 28: 796–803.
29.Jin Y, Chen J, Feng Z, et al. The expression of Survivin and NF-κB associated with prognostically worse clinicopathologic variables in hepatocellular carcinoma. Tumor Biol. 2014; 35: 9905–9910.
30.Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981; 29(4):577-80.
31. Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis – correlation in invasive breast carcinoma. N Engl J Med. 1991; 324(1):1-8.
32. Mandarim-de-Lacerda CA. Stereological tools in biomedical research. An Acad Bras Cienc. 2003; 75(4):469-86.
33. Lin F, Chen Z. Standardization of Diagnostic Immunohistochemistry. Arch Pathol Lab Med. 2014; 138:1564–1577.
34. Chodbury KR, Yagle KJ, Swanson PE, et al. A robust automated measure of average antibody staining in immunohistochemistry images. J Histochem Cytochem. 2010; 58(2):95-107.
35. Brey EM, Lalani Z, Johnston C, et al. Automated selection of DAB-labeled Tissue for Immunohistochemical Quantification. J Histochem Cytochem. 2003; 51(5):575-84.
36. Ruifrok AC, Johnston DA. Quantification of histochemical staining by color deconvolution. Anal Quant Cytol Histol. 2001; 23(4):291-9.
37. Buendia MA, Neuveut C. Hepatocellular carcinoma. Cold Spring Harb Perspect Med. 2015; 5(2): 021444.
38. Yang JD, Roberts LR. Hepatocellular carcinoma: a global view. Nat. Rev. Gastroenterol. Hepatol. 2010; 7:448–458.
39. CEVS - Rio Grande do Sul. Panorama das Hepatites Virais no Estado do Rio Grande do Sul, Brasil. [Internet] 2018. Available from: https://cevs.rs.gov.br/upload/arquivos/201807/25114428-panorama-das-hepatites-virais-b-e-c-no-rs.pdf.
40. Appel-da-Silva MC, Miozzo SAS, Dossin IA, et al. Incidence of hepatocellular carcinoma in outpatients with cirrhosis in Brazil: A 10-year retrospective cohort study. World J Gastroenterol. 2016; 22(46): 10219–10225.
41. Kikichu L, Chagas AL, Alencar RSSM, et al. Clinical and epidemiological aspects of hepatocellular carcinoma in Brazil. Antivir Ther. 2013;18(3 Pt B):445-9.
42. Kew MC. The role of cirrhosis in the etiology of hepatocellular carcinoma. J Gastrointest Cancer. 2014; 45 (1): 12-21.
43.Birgani MT, Carloni V. Tumor microenvironment, a paradigm in hepatocellular carcinoma progression and therapy. Int J Mol Sci. 2017; 18(2): 1-19.
44. Shimizu I, Kohno N, Tamaki K, et al. Female hepatology: Favorable role of estrogen in chronic liver disease with hepatitis B virus infection. World J Gastroenterol. 2007; 13(32): 4295-4305.
45. Visozo FJ, Rodriguez M, Altadill A, et al. Liver expression of steroid hormones and Apolipoprotein D receptors in hepatocellular carcinoma. World J Gastroenterol. 2007; 13(23): 3221-3227.
46. Hong EJ, Levasseur MP, Dufour CR, et al. Loss of estrogen-related receptor α promotes hepatocarcinogenesis development via metabolic and inflammatory disturbances. Proc Natl Acad Sci U S A. 2013; 110(44):17975-80.
47. Cui W, Yu CH, Hu KQ. In vitro and in vivo effects and mechanisms of celecoxib-induced growth inhibition of human hepatocellular carcinoma cells. Clin Cancer Res. 2005; 11(22):8213-21.
48. Morisaki T, Umebayashi M, Kiyota A, et al. Combining celecoxib with sorafenib synergistically inhibits hepatocellular carcinoma cells in vitro. Anticancer Res. 2013; 33(4):1387-95.
49. Wang H, Liu J, Hu X, et al. Prognostic and therapeutic values of tumor necrosis factor-alpha in hepatocellular carcinoma. Med Sci Monit. 2016; 22: 3694-3704.
50. Dong Y, Liu Y, Kou X, et al. The protective or damaging effect of Tumor necrosis factor‑α in acute liver injury is concentration‑dependent. Cell Biosci. 2016; 6 (8): 1-10.
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Alves A, Baldissera V, Chiela E, Cerski C, Fontes P, Fernandes M, et all. Altered expression of COX-2 and TNF-α in patients with hepatocellular carcinoma. 5898/2018


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Publication history

Received: 31/08/2018

Accepted: 22/11/2018

Online First: 27/02/2019

Published: 07/05/2019

Article revision time: 75 days

Article Online First time: 180 days

Article editing time: 249 days


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