Expression of p53 Protein in Colorectal Cancer and Association With Prognostic Factors in Northeast Iran
AbstractColorectal cancer (CRC) is one of the most prevalent cancers in the world. The p53 protein is the most commonly mutated protein in human cancer, and it is a frequent abnormality in colorectal cancers. In this study, we evaluated the expression of p53 protein and its association with clinicopathological findings as prognostic factors and mortality rate in 95 colorectal cancer patients’ in Northeast Iran, over a 5 years period (2010-2015). In this retrospective study, the method of immunohistochemistry (IHC) was applied to determine the expression of the p53 protein and pathological features of tumors and mortality rate were examined between 2010 and 2015 at Gorgan City (IRAN). Multiple logistic regression models were used to estimate odds ratios and confidence intervals between clinicopathological and mortality rate as the outcome variable, adjusted for potential confounders. Immunoreactivity was found in 58.9% of specimens from 95 patients with colorectal cancer, and the mortality rate was estimated 14.7 percent. The mortality rate of patients with colorectal cancer is significant, and findings indicate that it relates to pathologic factors such as vascular involvement [OR=0.02, CI95%: 0.006-0.11], lymph node involvement [OR=0.17, CI95%: 0.05-0.56], round neural invasion, depth of invasion, tumor size and grade. The findings confirmed that the P53 gene mutation could be considered as a prognostic factor affecting mortality in cancer and specifically colorectal cancer. Although the P53 protein expression shows no relationship with histopathological features, the mortality rate of the patients demonstrated a strong association.
Schreuders EH, Ruco A, Rabeneck L, Schoen RE, Sung JJ, Young GP, et al. Colorectal cancer screening: a global overview of existing programmes. Gut 2015;64:1637-49.
Dolatkhah R, Somi MH, Bonyadi MJ, Asvadi Kermani I, Farassati F, Dastgiri S. Colorectal cancer in Iran: molecular epidemiology and screening strategies. J Cancer Epidemiol 2015;2015:643020.
Vousden KH, Lane DP. P53 in health and disease. Nat Rev Mol Cell Biol 2007;8:275-83.
Lima CRdO, Rabelo RE, Vulcani VAS, Cardoso LD, Sousa NLdM, Moura VMBDd. P53 gene: major mutations in neoplasias and anticancer gene therapy. Ciência Rural 2012;42:845-53.
Al-Salihi KA, Azlina A. P53 gene mutation and protein expression in ameloblastomas. Braz J Oral Sci 2015;5:1034-40.
Olivier M, Hollstein M, Hainaut P. TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol 2010;2:a001008.
Rivlin N, Brosh R, Oren M, Rotter V. Mutations in the p53 tumor suppressor gene important milestones at the various steps of tumorigenesis. Genes Cancer 2011;2:466-74.
Muller PA, Vousden KH. p53 mutations in cancer. Nat Cell Biol 2013;15:2-8.
Duffy M, Van Dalen A, Haglund C, Hansson L, Holinski-Feder E, Klapdor R, et al. Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use. Eur J Cancer 2007;43:1348-60.
Pages F, Galon J, Dieu-Nosjean M, Tartour E, Sautes-Fridman C, Fridman W. Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene 2010;29:1093-102.
Mehravar F, Rafiee S, Bazrafshan B, Khodadost M. Prevalence of asthma symptoms in Golestan schoolchildren aged 6–7 and 13–14 years in Northeast Iran. Front Med 2016;10:345-50.
Akkiprik M, Ataizi-Celikel C, Dusunceli F, Sonmez O, Gulluodlu BM, Sav A, et al. Clinical significance of p53, K-ras and DCC gene alterations in the stage I-II colorectal cancers. J Gastrointestin Liver Dis 2007;16:11.
Zhao D-p, Ding X-w, Peng J-p, Zheng Y-x, Zhang S-z. Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma. J Zhejiang Univ Sci B 2005;6:1163-9.
Bazan V, Agnese V, Corsale S, Calo V, Valerio M, Latteri M, et al. Specific TP53 and/or Ki-ras mutations as independent predictors of clinical outcome in sporadic colorectal adenocarcinomas: results of a 5-year Gruppo Oncologico dell'Italia Meridionale (GOIM) prospective study. Ann Oncol 2005;16:iv50-iv5.
Russo A, Bazan V, Iacopetta B, Kerr D, Soussi T, Gebbia N. The TP53 colorectal cancer international collaborative study on the prognostic and predictive significance of p53 mutation: influence of tumor site, type of mutation, and adjuvant treatment. J Clin Oncol 2005;23:7518-28.
Ren J, Li G, Ge J, Li X, Zhao Y. Is K-ras gene mutation a prognostic factor for colorectal cancer: a systematic review and meta-analysis. Dis Colon Rectum 2012;55:913-23.
Mahdavinia M, Bishehsari F, Verginelli F, Cumashi A, Lattanzio R, Sotoudeh M, et al. P53 mutations in colorectal cancer from northern Iran: Relationships with site of tumor origin, microsatellite instability and K ras mutations. J Cell Physiol 2008;216:543-50.
Golmohammadi R, Namazi MJ, Nikbakht M, Salehi M, Derakhshan MH. Characterization and prognostic value of mutations in exons 5 and 6 of the p53 gene in patients with colorectal cancers in central Iran. Gut Liver 2013;7:295-302.
Zu Y, Steinberg SM, Campo E, Hans CP, Weisenburger DD, Braziel RM, et al. Validation of tissue microarray immunohistochemistry staining and interpretation in diffuse large B-cell lymphoma. Leuk Lymphoma 2005;46:693-701.
Zlobec I, Steele R, Michel RP, Compton CC, Lugli A, Jass JR. Scoring of p53, VEGF, Bcl-2 and APAF-1 immunohistochemistry and interobserver reliability in colorectal cancer. Mod Pathol 2006;19:1236-42.
Malekzadeh R, Bishehsari F, Mahdavinia M, Ansari R. Epidemiology and molecular genetics of colorectal cancer in Iran: a review. Arch Iran Med 2009;12:161-9.
Munro A, Lain S, Lane D. P53 abnormalities and outcomes in colorectal cancer: a systematic review. Br J Cancer 2005;92:434-44.
Zaanan A, Cuilliere-Dartigues P, Guilloux A, Parc Y, Louvet C, De Gramont A, et al. Impact of p53 expression and microsatellite instability on stage III colon cancer disease-free survival in patients treated by 5-fluorouracil and leucovorin with or without oxaliplatin. Ann Oncol 2010;21:772-80.
Heer Pd. Molecular and biological interactions in colorectal cancer [Dissertation]. Netherlands: Leiden Univ., 2007.
Zhang M-F, Zhang Z-Y, Fu J, Yang Y-F, Yun J-P. Correlation between expression of p53, p21/WAF1, and MDM2 proteins and their prognostic significance in primary hepatocellular carcinoma. J Trans Med 2009;7:110.
Marmot M, Atinmo T, Byers T, Chen J, Hirohata T, Jackson A, et al. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. (Accessed January 2018, 2, at http://www.aicr.org/assets/docs/pdf/ reports/Second_Expert_Report.pdf).
Levin B, Lieberman DA, McFarland B, Smith RA, Brooks D, Andrews KS, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin 2008;58:130-60.
Haggar FA, Boushey RP. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg 2009;22:191-7.
Gonzalez M, Poncet A, Combescure C, Robert J, Ris HB, Gervaz P. Risk factors for survival after lung metastasectomy in colorectal cancer patients: a systematic review and meta-analysis. Ann Surg Oncol 2013;20:572-9.