Immunohistochemical Expression of p53 and bcl2 in Colorectal Adenomas and Carcinomas Using Automated Cellular Imaging System

Document Type: Original Research

Authors

Dept. of Pathology and Forensic Medicine, Al-Nahrain University, Baghdad, Iraq

Abstract

Background & Objective: The current approaches to reduce the risk of colorectal carcinoma are through the detection and removal of the precursor lesion” adenomatous polyps”. The study was conducted to evaluate the immunohistochemical expression of p53 and bcl2 in colorectal adenomas and carcinomas.
Patients and Methods: A total of 86 cases, 33 colorectal adenomas, 33 colorectal adenocarcinomas and 20 samples of non -tumerous colonic tissue as control, were included in this retrospective study. Sections were stained immunohistochemically for p53 and bcl2. Scoring was performed using Digimizer software. Data were analyzed using SPSS program (Statistical Package for Social Sciences) version 16 and Microsoft Office Excel 2007.
Results: The frequency of p53 positive cases was significantly higher in carcinoma than adenoma while the frequency of bcl2 positive cases was significantly higher in adenoma than carcinoma. P53 expression was significantly higher in large sized adenomas, villous configuration, severe dysplasia, and multiple lesions. Bcl2 expression showed significantly correlated with adenomas of small size, solitary, tubular, and mild dysplasia. There was a significant correlation between bcl2 expression and non-mucinous carcinoma and a negative correlation with tumor size.Therewas an inverse relationship between bcl2 and p53 expression in both colorectal adenomas and carcinomas.
 

Keywords


  1. Takahashi M, Wakabayashi K. Gene mutations and altered gene expression in azoxymethane-induced colon carcinogenesis in rodents. Cancer Sci 2004;95(6):475-80.
  2. Calvert PM , Frucht H. The genetics of colorectal cancer. Ann Intern Med 2002;137(7):603-12.
  3. Morán A, Ortega P, de Juan C, Fernández-Marcelo T, Frías C, Sánchez-Pernaute A,  et al. Differential colorectal carcinogenesis: molecular basis and clinical relevance. World J Gastrointest Oncol 2010;2(3):151-8.
  4. Ozaki T, Nakagawara A. p53: the attractive tumor suppressor in the cancer research field. J Biomed Biotechnol 2011;2011:603925.
  5. Menezes HL, Jucá MJ, Gomes EG, Nunes BL, Costa HO, 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 2010;47(2):141-7.
  6. Zavrides H, Zizi-Sermpetzoglou A, Elemenoglou I, Papatheofanis I, Peros G, Athanasas G,  et al. Immunohistochemical expression of bcl-2 in UICC stage I and III colorectal carcinoma patients: correlation with c-erbB-2, p53, ki-67, CD44, laminin and collagen IV in evaluating prognostic significance. Pol J Pathol 2006;57(3):149-59.
  7. Saneei MH, Razi M. Role of bcl2 oncoprotein in carcinogenesis of colorectal neoplasia and its correlation with histopathologic and prognostic parameter. Journal of Isfahan Medical School 2005;23(78):30-6.
  8. Yan-fang A, Yong M, Jing-hua L. The expressions of PCNA and Bcl-2 in colorectal adenoma and carcinoma and their clinicopathological and prognostic significance. Acta Academiae Medicinae Xuzhou 2006;6:11-7.
  9. Contu PC, Contu SS, Moreira LF. Bcl-2 expression in rectal cancer. Arq Gastroenterol 2006; 43(4):284-7.
  10. Ishii T, Notohara K, Umapathy A, Mallitt KA, Chikuba H, Moritani Y, et al. Tubular adenomas with minor villous changes show molecular features characteristic of tubulovillous adenomas. Am J Surg Pathol 2011;35(2):212-20.
  11. Sheikh RA, Min BH, Yasmeen S, Teplitz R, Tesluk H, Ruebner BH,  et al. Correlation of Ki-67, p53, and Adnab-9 immunohistochemical staining and ploidy with clinical and histopathologic features of severely dysplastic colorectal adenomas. Dig Dis Sci 2003;48(1):223-9.
  12. Tzouvala M, Lazaris AC, Papatheodoridis GV, Kouvidou C, Papathomas TG, Kavantzas N,  et al. Potential role of apoptosis and apoptotic regulatory proteins in colorectal neoplasia: correlations with clinico-pathological parameters and survival. Dig Dis Sci 2008;53(2):451-60.
  13. Vernillo R, Lorenzi B, Banducci T, Minacci C, Vindigni C, Lucenti Fei A , et al. Immunohistochemical expression of p53 and Ki67 in colorectal adenomas and prediction of malignancy and development of new polyps. Int J Biol Markers 2008;23(2):89-95.
  14. Einspahr JG, Martinez ME, Jiang R, Hsu CH, Rashid A, Bhattacharrya AK,  et al. Associations of Ki-ras proto-oncogene mutation and p53 gene overexpression in sporadic colorectal adenomas with demographic and clinicopathologic characteristics. Cancer Epidemiol Biomarkers Prev 2006;15(8):1443-50.
  15. Nussrat FL, Ali HH, Hussein HG,AL-Ukashi RJ. Immunohistochemical expression of ki-67 and p53 in colorectal adenomas: a clinicopathological study. Oman Med J 2011;26(4):229-234.
  16. Abdulamir AS, Hafidh R, Mahdi L, Al-jeboori L, Abubaker F, Abbas KA. The interplay between p53 and p21 tumor suppressor proteins in the transformation of colorectal adenoma to carcinoma. Am J Immunol 2008;4:14-22.
  17. Mulder JW, Wielenga VJ, Polak MM, van den Berg FM, Adolf GR, Herrlich P,  et al. Expression of mutant p53 protein and CD44 variant proteins in colorectal tumorigenesis. Gut 1995;36(1):76-80.
  18. Gurzu S, Jung J, Mezei T, Pavai Z. The correlation between the immunostains for p53 and Ki67 with bcl-2 expression and classical prognostic factors in colorectal carcinomas. Rom J Morphol Embryol 2007;48(2):95-9.
  19. Ghavam-Nasiri MR, Rezaei E, Ghafarzadegan K, Seilanian-Toosi M, Malekifard H. Expression of p53 in colorectal carcinoma: correlation with clinicopathologic features. Arch Iranian Med 2007;10(1):38-42.
  20. Nancy Y, Assad MD, Mona A. Prognostic value of Cyclin D1 and p53 protein in colorectal carcinoma. Cancer Institute 2000;12:283-92.
  21. Soong R, Powell B, Elsaleh H, Gnanasampanthan G, Smith DR, Goh HS,  et al. Prognostic significance of TP53 gene mutation in 995 cases of colorectal carcinoma. Influence of tumor site, stage, adjuvant chemotherapy, and type of mutation. Eur J Cancer 2000;36(16):2053-60.
  22. Gervaz P, Bouzourene H, Cerottini JP, Chaubert P, Benhattar J, Secic M,  et al. Dukes B colorectal cancer: distinct genetic categories and clinical outcome based on proximal or distal tumor location. Dis Colon Rectum 2001;44(3):372-3.
  23. Lanza G Jr, Maestri I, Dubini A, Gafa R, Santini A, Ferretti S,  et al. P53 expression in colorectal cancer: relation to tumor type, DNA ploidy pattern, and shortterm survival. Am J Clin Pathol 1996;105(5):604-12.
  24. Garrity MM, Burgart LJ, Mahoney MR, Windschitl HE, Salim M, Wiesenfeld M,  et al. Prognostic value of proliferation, apoptosis, defective DNA mismatch repair, and p53 overexpression in patients with resected Dukes' B2 or C colon cancer: a North Central Cancer Treatment Group Study. J Clin Oncol 2004;22(9):1572-82.
  25. Sinicrope FA, Ruan SB, Cleary KR, Stephens LC, Lee JJ, Levin B. bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. Cancer Res 1995;55(2):237-41.
  26. Saleh HA, Jackson H, Banerjee M. Immunohistochemical expression of bcl-2 and p53 oncoproteins: correlation with Ki67 proliferation index and prognostic histopathologic parameters in colorectal neoplasia. Appl Immunohistochem Mol Morphol 2000;8(3):175-82.
  27. Yang HB, Chow NH, Sheu BS, Chan SH, Chien CH, Su IJ. The role of bcl-2 in the progression of the colorectal adenoma-carcinoma sequence. Anticancer Res 1999;19(1B):727-30.
  28. Hussain AG. bcl2 overexpression in colorectal carcinoma. Iraqi J Med Sci 2008;6:66-76.
  29. Demirbaş S, Sücüllü I, Yildirim S, Celenk T. Influence of the c-erb B-2, nm23, bcl-2 and p53 protein markers on colorectal cancer. Turk J Gastroenterol 2006;17(1):13-9.