Scientific Online Resource System

Varna Medical Forum

P53 Expression In Colorectal Epithelial Neoplasms And Its Relation To Clinical And Histopathological Features

Nedyalka Zgurova, Maria Tzaneva


Introduction: Colorectal carcinoma (CRC) is the result of genetic and epigenetic disorders. The p53 gene, known as the guardian of the genome, plays an important role in apoptosis and inhibition of angiogenesis.

Aim: The aim of our study is to investigate and compare the expression of p53 in the tumor tissue of synchronous/metachronous adenomas and CRC and its relation to clinical and histopathological features, and to evaluate p53 as a predictive marker.

Materials and Methods: Materials from 18 synchronous/metachronous colorectal adenomas and 21 CRCs were fixed in formalin (10% neutral), followed by paraffin embedding of tissue. Tissue sections of 5 μ were stained with hematoxylin and eosin to evaluate histological parameters. For immunohistochemistry, the monoclonal rabbit p53 antibody (Clone Y5) was used. A five-step scale was used to evaluate the percentage of positive nuclear expression: 0 (0-5%), 1 (6-25%), 2 (26-50%) and 3 (51-75%) and 4 (>75%).

Results: Seven (38.89%) of the benign neoplasms were positive for p53 and the expression of the protein was in correlation with size, localization in the right half of the colon and the villous component of the adenoma, and inversely dependent on its differentiation degree (p <0.05). Tumor tissue of 13 (61.90%) CRCs accumulated p53, but there was no correlation with clinical and morphological parameters: age, gender, size, localization, TNM stage and grade of differentiation (p>0.05). The non-neoplastic colonic mucosa was negative in all cases.

Conclusion: Accumulation of p53 is a predictor of malignancy in colorectal adenoma and plays part in adenoma-carcinoma tumor progression.


p53, synchronous/metachronous adeno-mas, colorectal carcinoma, clinical-morphological parameters

Full Text


Георгиева М, Тончева Д. Молекулярно-генетичен скрининг на нефамилен и фамилен колоректален и анален карцином. УЧЕБНА КНИГА МОРЕ, 2011. Поведение при колоректален и анален карцином Танграм медия ООД 7-14

Adrover E, M L Maestro ML, Sanz-Casla MT, del Barco V, Cerdán J, Fernández C, Balibrea JL. Expression of high p53 levels in colorectal cancer: a favourable prognostic factor. Br J Cancer. 1999;81(1):122–126

Akshatha C, Mysorekar V,Arundhathi S, Arul P, Adithi Raj,Smitha Shetty. Correlation of p53 Overexpression with the Clinicopathological Prognostic Factors in Colorectal Adenocarcinoma. J Clin Diagn Res. 2016;10(12): EC05–EC08.

Ananiev J, Tchernev G, Patterson JW, Gulubova M, Ganchev G. р53 – “the guardian of genome. Acta Medica Bulgarica. 2011;38:72-82.

Arnold M, Sierra M,Laversanne M, Soerjomataram I,Jemal A, Bray FR. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683-691.

Bond JH. Polyp guideline: diagnosis, treatment, and surveillance for patients with colorectal polyps. Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol. 2000;95:3053-3063

Bourdon JC, Fernandes K, Murray-Zmijewski F, Liu G, Diot A, Xirodimas DP, Saville MK, Lane DP. p53 isoforms can regulate p53 transcriptional activity". Genes & Development. 2005;19(18):2122–2137.

Cao DZ, Ou XL, Yu T. The association of p53 expression levels with clinicopathological features and prognosis of patients with colon cancer following surgery. Oncol Lett. 2017;13(5):3538–3546

Colomer A, Erill N, Verdm M, et al. Lack of p53 nuclear immunostaining is not indicative of absence of TP53 gene mutation in colorectal adenocarcinomas. Appl immunohistochemistry and Molecular Morphology. 2003;11:130–137

Contu PC, Contu SS, and Moreira LF. Bcl-2 expression in rectal cancer. Arq Gastroenterol. 2006;43:284-87.

Di Gregorio C, Bonetti LR, de Gaetani C, Pedroni M, Kaleci S, Ponz de Leon M. Clinical outcome of low- and high-risk malignant colorectal polyps: results of a population-based study and meta-analysis of the available literature. Intern Emerg Med. 2014 Mar;9(2):151-60

Favoriti P, Carbone G, Greco M, Pirozzi F, Pirozzi RE, Corcione F. Worldwide burden of colorectal cancer: a review. Updates Surg. 2016;68(1):7-11

Ghita C, Vilcea ID, Dumitrescu M, Vilcea AM, Mirea CS, Aschie M, et al. The prognostic value of the immunohistochemical aspects of tumour suppressor genes p53, bcl-2, PTEN and nuclear proliferative antigen Ki-67 in resected colorectal carcinoma. Rom J Morphol Embryol . 2012;53:549-56

Gurzu S, Jung J, Mezei T, Pávai 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):95-99.

Huang C, Cheng Y, Chen M, Lin S, Chou M, Lee H. Different p53 mutation patterns in colorectal tumors from smokers and nonsmokers. Environmental and Molecular mutagenesis. 2006;47:527–532.

Iordache S, Saftoiu A, Ciurea T, Georgescu CV, Chilusi M. Predictive parametres for advanced neoplastic adenomas and colorectal cancer in patients with colonic polyos – a study in a tertiary medical centre in the South-West region of Romania. Romanian J Morphology Embryology 2006;47(3):239-243.

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

Jerjees DA, Bedoor A, Irhayim-AL. P53 expression in colonic carcinoma –immunohistochemical study. Ann Coll Med Mosul.2009;35:111-16

Kaklamanis L, Gatter KC, Mortensen N, Baigrie RJ, Heryet A, Lane DP, Harris AL. p53 expression in colorectal adenomas. Am J Pathol. 1993;142(1):87-93.

Kapiteiijn E, Liefers G, Los L, et al. Mechanisms of oncogenesis in colon versus rectal cancer. J Pathol. 2001;195:171–178

Kruschewski M, Mueller K, Lipka S, Budczies J, Noske A, Buhr HJ, Elezkurtaj S. The Prognostic Impact of p53 Expression on Sporadic Colorectal Cancer Is Dependent on p21 Status. Cancers (Basel). 2011;3(1): 1274–1284

Liang JT, Huang KC, Cheng YM, Hsu HC, Cheng AL, Hsu CH, et al. P53 overexpression predicts poor chemosensitivity to high-dose 5-fluorouracil plus leucovorin chemotherapy for stage IV colorectal cancers after palliative bowel resection. Int J Cancer 2002;97:451–457.

Matsuda K, Masaki T and Watanbe T. Clinical significance of MUC1 and MUC2 mucin and p53 protein expression in colorectal carcinoma. Japanese Journal of Clinical Oncology. 2000;30:89-94.

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):151-158.

Nassierowsken-Guttmejer A, Treeciale L, Nowacki MP, Ostrowsk J. p53 protein accumulation and p53 gene mutation in colorectal cancer. Path Oncol Res. 2000;6:275–279

Paluszkiewicz P, Berbec H, Pawlowska-Wakowicz B, Cybulski M, Paszkowska A. p53 protein accumulation in colorectal cancer tissue has prognostic value only in left-sided colon tumours. Cancer Detect Prev. 2004;28:252–259.

PraSad GR, Banda S. Evaluation of Immunoreactivity of p53 in Colorectal Adenocarcinomas. National Journal of Laboratory Medicine 2017;6(1):28 – 32.

Qasim B, Husam Ali, Alaa Hussein Immunohistochemical Expression of p53 and bcl-2 inColorectal Adenomas and Carcinomas Using Automated Cellular Imaging System Iranian Journal of Pathology. 2012;7(4):215 – 223.

Rambau PF, Odida M, and Wabinga H. p53 expression in colorectal carcinoma in relation to histopathological features in Ugandan patients. Afr Health Sci. 2008 Dec; 8(4): 234–238.

Servomaa K, Kosma V-M, Hirvikoski P, Rytömaa T. p53 and K-ras mutations in carcinoma of the rectum among Finish women. J Clin Pathol: Mol Pathol. 2000;53:24–30.

Sharifi N, Sharifi K, Ayatollahi H, Shakeri MT, Sadeghian MH and Azari JB. Evaluation of angiogenesis in colorectal carcinoma by CD34 immunohistochemistry method and its correlation with clinicopathologic parameters. Acta Medica Iranica. 2009;47:161-164

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):223-229

Slattery ML, Ballard-Barbash R, Potter JD, Ma KN, Caan BJ, Anderson K, et al. Sex-specific differences in colon cancer associated with p53 mutations. Nutr Cancer.2004;49:41–48

Wang P, Liang J, Wang Z, Hou H, Shi L, Zhou Z. The prognostic value of p53 positive in colorectal cancer: A retrospective cohort study.Tumour Biol. 2017;39(5): 1010428317703651.

Xi HQ, Zhang KE, Li JY, Cui JX, Zhao P, Chen L. Expression and clinicopathologic significance of TUFM and p53 for the normal–adenoma–carcinoma sequence in colorectal epithelia. World Journal of Surgical Oncology 2017;15(1):15:90

Zhao D, Ding X, Peng J, Zheng Y, Zhang S. Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma. Journal of Zhejiang University. 2005;6:1163–1169


Font Size