B-cell lymphoma 2 and β-catenin expression in colorectal cancer and their prognostic role following surgery

Balzi,Manuela; Ringressi,Maria  Novella; Faraoni,Paola; Booth,Catherine; Taddei,Antonio; Boni,Luca; Bechi,Paolo

doi:10.3892/mmr.2015.3385

B-cell lymphoma 2 and β-catenin expression in colorectal cancer and their prognostic role following surgery

Authors:
- Manuela Balzi
- Maria Novella Ringressi
- Paola Faraoni
- Catherine Booth
- Antonio Taddei
- Luca Boni
- Paolo Bechi
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Affiliations: Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence 50139, Italy, Department of Surgery and Translational Medicine, University of Florence, Florence 50134, Italy, Epistem Limited, Incubator Building, Manchester M13 9XX, United Kingdom, Clinical Trials Coordinating Center, Careggi Hospital and Tumour Institute of Tuscany, Florence 50134, Italy
Published online on: February 24, 2015 https://doi.org/10.3892/mmr.2015.3385
Pages: 553-560

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Abstract

The prognosis of colorectal cancer depends on the stage of the disease. However, even within the same stage there may be different outcomes in terms of recurrence and survival. Therefore, it is clear that as well as pathological stage, novel biomarkers that are capable of improving risk stratification and therapeutic decision‑making are required. The present study aimed to evaluate the potential roles of two previously proposed biomarkers of tumour status: B‑cell lymphoma 2 (Bcl‑2) and β‑catenin. A total of 412 patients undergoing surgery for primary colorectal cancer were studied. Tumour specimens of the patients were collected, fixed and processed for immunohistochemical detection of Bcl‑2 and β‑catenin. The data were then analyzed in relation to disease‑free survival and overall survival. Pathological stage was the only variable that was significantly correlated with both disease‑free and overall survival. The expression levels of neither Bcl‑2 nor β‑catenin were able to accurately predict prognosis. However, there was a clear association between nuclear β‑catenin expression levels and disease‑free survival in the three tumour stages. There was an increased hazard ratio in stage I and II nuclear β‑catenin positive tumours, whereas there was a marked decrease in risk in stage III positive tumours. A similar effect was also observed with regards to overall survival, however this finding was not significant. The results of the present study suggest that conventional pathological tumour staging is the only accurate prognostic method. Neither Bcl‑2 or β‑catenin were shown to be useful biomarkers for the prognosis of colorectal cancer. However, the heterogeneous behaviour of nuclear β‑catenin expression in the various tumour stages may indicate a possible role in predicting the response of patients to chemotherapy. Therefore, nuclear β‑catenin expression may be a biomarker for the prediction of improved responses to chemotherapy.

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1	von Karsa L, Anttila A, Ronco G, Ponti A, Malila N, Arbyn M, et al: Cancer screening in the European Union-Report on the implementation of the Council Recommendation on cancer screening. First Report. International Agency for Research on Cancer. European Communities; 2008
2	Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 (Internet). Lyon, France: International Agency for Research on Cancer. Available from: http://globocan.iarc.fr.
3	Zhou Z, Wu X, Wang R, Li L, Lu Z, Chen G, et al: Optimal use of adjuvant chemotherapy in stage II colorectal cancer. Int J Colorectal Dis. 26:867–873. 2011. View Article : Google Scholar : PubMed/NCBI
4	QUASAR Collaborative Group; Gray R, Barnwell J, McConkey C, Hills RK, Williams NS and Kerr DJ: Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 370:2020–2029. 2007. View Article : Google Scholar : PubMed/NCBI
5	Quah HM, Chou JF, Gonen M, Shia J, Schrag D, Landmann RG, et al: Identification of patients with high-risk stage II colon cancer for adjuvant therapy. Dis Colon Rectum. 51:503–507. 2008. View Article : Google Scholar : PubMed/NCBI
6	Gertler R, Rosenberg R, Schuster T and Friess H: Defining a high-risk subgroup with colon cancer stages I and II for possible adjuvant therapy. Eur J Cancer. 45:2992–2999. 2009. View Article : Google Scholar : PubMed/NCBI
7	Fearon ER and Vogelstein B: A genetic model for colorectal tumourigenesis. Cell. 61:759–767. 1990. View Article : Google Scholar : PubMed/NCBI
8	Strasser A, Huang DC and Vaux DL: The role of the bcl-2/ced-9 gene family in cancer and general implications of defects in cell death control for tumourigenesis and resistance to chemotherapy. Biochim Biophys Acta. 1333:151–178. 1997.
9	Armaghany T, Wilson JD and Mills G: Genetic alterations in colorectal cancer. Gastrointest Cancer Res. 5:19–27. 2012.PubMed/NCBI
10	Fodde R and Tomlinson I: Nuclear beta-catenin expression and Wnt signalling: in defence of the dogma. J Pathol. 221:239–241. 2010. View Article : Google Scholar : PubMed/NCBI
11	Wang Z and Ma Q: Beta-catenin is a promising key factor in the SDF-1/CXCR4 axis on metastasis of pancreatic cancer. Med Hypotheses. 69:816–820. 2007. View Article : Google Scholar : PubMed/NCBI
12	Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL and Trotti A: AJCC Cancer Staging Manual and Handbook. 7th edition. Springer; New York: 2010
13	Schemper M and Smith TL: A note on quantifying follow-up in studies of failure time. Control Clin Trials. 17:343–346. 1996. View Article : Google Scholar : PubMed/NCBI
14	Labianca R, Nordlinger B, Beretta GD, Mosconi S, Mandalà M and Cervantes A: Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 24(Suppl 6): 64–72. 2013. View Article : Google Scholar
15	Becciolini A, Porciani S, Balzi M, Lanini A, Scubla E, Pacini P, et al: Cell kinetics and biochemical parameters in breast cancer. Int J Biol Markers. 7:16–20. 1992.PubMed/NCBI
16	Becciolini A, Balzi M, Boanini P, Maugeri A, Pacini P, Bianchi S, et al: Cell kinetics in breast cancer. In Vivo. 7:627–629. 1993.PubMed/NCBI
17	Medri L, Nanni O, Volpi A, Scarpi E, Dubini A, Riccobon A, et al: Angiogenesis in breast cancer. Eur J Oncol. 7:185–189. 2002.
18	Watson AJ, Merritt AJ, Jones LS, Askew JN, Anderson E, Becciolini A, et al: Evidence for reciprocity of bcl-2 and p53 expression in human colorectal adenomas and carcinomas. Br J Cancer. 73:889–895. 1996. View Article : Google Scholar : PubMed/NCBI
19	Becciolini A, Balzi M, Faraoni P, Tisti E, Zappoli Thyrion G, Giachè V, et al: Colonic cell proliferation in normal mucosa of patients with colon cancer. Acta Oncol. 37:65–71. 1998. View Article : Google Scholar : PubMed/NCBI
20	Cianchi F, Balzi M, Becciolini A, Giachè V, Messerini L, Palomba A, et al: Correlation between DNA content and p53 deletion in colorectal cancer. Eur J Surg. 165:363–368. 1999. View Article : Google Scholar : PubMed/NCBI
21	Wilson JW, Nostro MC, Balzi M, Faraoni P, Cianchi F, Becciolini A, et al: Bcl-w expression in colorectal adenocarcinoma. Br J Cancer. 82:178–185. 2000. View Article : Google Scholar : PubMed/NCBI
22	Wilson JW, Deed RW, Inoue T, Balzi M, Becciolini A, Faraoni P, et al: Expression of Id helix-loop-helix proteins in colorectal adenocarcinoma correlates with p53 expression and mitotic index. Cancer Res. 61:8803–8810. 2001.PubMed/NCBI
23	Volpi A, De Paola F, Nanni O, Granato AM, Bajorko P, Becciolini A, et al: Prognostic significance of biological markers in node-negative breast cancer patients: a prospective study. Breast Cancer Res Treat. 63:181–192. 2000. View Article : Google Scholar : PubMed/NCBI
24	Balzi M, Ninu MB, Becciolini A, Scubla E, Boanini P, Gallina E, et al: Labeling index in squamous cell carcinoma of the larynx. Head Neck. 13:344–348. 1991. View Article : Google Scholar : PubMed/NCBI
25	Muraro GB, Melone F, Farina U, Balzi M and Becciolini A: Adjuvant therapy with BCG in superficial bladder cancer selected by proliferative activity assessment. J Chemother. 8S4:328–330. 1996.
26	Zhao DP, Ding XW, Peng JP, Zheng YX and Zhang SZ: Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma. J Zhejiang Univ Sci B. 6:1163–1169. 2005. View Article : Google Scholar : PubMed/NCBI
27	Manne U, Myers RB, Moron C, Poczatek RB, Dillard S, Weiss H, et al: Prognostic significance of Bcl-2 expression and p53 nuclear accumulation in colorectal adenocarcinoma. Int J Cancer. 74:346–358. 1997. View Article : Google Scholar : PubMed/NCBI
28	Bosari S, Moneghini L, Graziani D, Lee AK, Murray JJ, Coggi G, et al: bcl-2 oncoprotein in colorectal hyperplastic polyps, adenomas, and adenocarcinomas. Hum Pathol. 26:534–540. 1995. View Article : Google Scholar : PubMed/NCBI
29	Menezes HL, Jucá MJ, Gomes EG, Nunes BL, Costa HO and Matos D: Analysis of the immunohistochemical expressions of p53, bcl-2 and Ki-67 in colorectal adenocarcinoma and their correlations with the prognostic factors. Arq Gastroenterol. 47:141–147. 2010.In Portuguese. View Article : Google Scholar : PubMed/NCBI
30	Markowitz SD and Bertagnolli MM: Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med. 361:2449–2460. 2009. View Article : Google Scholar : PubMed/NCBI
31	Hugh TJ, Dillon SA, Taylor BA, Pignatelli M, Poston GJ and Kinsella AR: Cadherin-catenin expression in primary colorectal cancer: a survival analysis. Br J Cancer. 80:1046–1051. 1999. View Article : Google Scholar : PubMed/NCBI
32	Pancione M, Forte N, Sabatino L, Tomaselli E, Parente D, Febbraro A, et al: Reduced beta-catenin and peroxisome proliferator-activated receptor-gamma expression levels are associated with colorectal cancer metastatic progression: correlation with tumour-associated macrophages, cyclooxygenase 2 and patient outcome. Hum Pathol. 40:714–725. 2009. View Article : Google Scholar : PubMed/NCBI
33	Wong SC, Lo ES, Chan AK, Lee KC and Hsiao WL: Nuclear beta-catenin as a potential prognostic and diagnostic marker in patients with colorectal cancer from Hong Kong. Mol Pathol. 56:347–352. 2003. View Article : Google Scholar : PubMed/NCBI
34	Wong SC, Lo ES, Chan JK and Hsiao WL: Prognostic and diagnostic significance of beta-catenin nuclear immunostaining in colorectal cancer. Clin Cancer Res. 10:1401–1408. 2004. View Article : Google Scholar : PubMed/NCBI
35	Tatsuguchi A, Kishida T, Fujimori S, Tanaka S, Gudis K, Shinji S, et al: Differential expression of cyclo-oxygenase-2 and nuclear β-catenin in colorectal cancer tissue. Aliment Pharmacol Ther. 24(Suppl. 4): 153–159. 2006. View Article : Google Scholar
36	Matsuoka T, Mitomi H, Fukui N, Kanazawa H, Saito T, Hayashi T, et al: Cluster analysis of claudin-1 and -4, E-cadherin, and β-catenin expression in colorectal cancers. J Surg Oncol. 103:674–686. 2011. View Article : Google Scholar : PubMed/NCBI
37	Ikeguchi M, Makino M and Kaibara N: Clinical significance of E-cadherin-catenin complex expression in metastatic foci of colorectal carcinoma. J Surg Oncol. 77:201–207. 2001. View Article : Google Scholar : PubMed/NCBI
38	Günther K, Brabletz T, Kraus C, Dworak O, Reymond MA, Jung A, et al: Predictive value of nuclear beta-catenin expression for the occurrence of distant metastases in rectal cancer. Dis Colon Rectum. 41:1256–1261. 1998. View Article : Google Scholar : PubMed/NCBI
39	Chung GG, Provost E, Kielhorn EP, Charette LA, Smith BL and Rimm DL: Tissue microarray analysis of beta-catenin in colorectal cancer shows nuclear phospho-beta-catenin is associated with a better prognosis. Clin Cancer Res. 7:4013–4020. 2001.PubMed/NCBI
40	Zeilstra J, Joosten SPJ, Wensveen FM, Dessing MC, Schütze DM, Eldering E, et al: WNT signaling controls expression of pro-apoptotic BOK and BAX in intestinal cancer. Biochem Biophys Res Commun. 406:1–6. 2011. View Article : Google Scholar
41	Bonadonna G, Robustelli Della, Cuna G and Valagussa P: Medicina Oncologica. Milano: Elsevier; 2007