Brief Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2010; 2(7): 295-303
Published online Jul 15, 2010. doi: 10.4251/wjgo.v2.i7.295
Aberrant promoter methylation of p16 in colorectal adenocarcinoma in North Indian patients
Pooja Malhotra, Rakesh Kochhar, Kim Vaiphei, Jai Dev Wig, Safrun Mahmood
Pooja Malhotra, Rakesh Kochhar, Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
Kim Vaiphei, Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
Jai Dev Wig, Department of General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
Safrun Mahmood, Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
Author contributions: Malhotra P performed the research, analyzed the data and drafted the manuscript; Kochhar R and Mahmood S participated in its design, coordination and helped to draft the manuscript; Vaiphei K analyzed the immunohistochemical part of the study and Wig JD provided the tissue specimens and all the clinical information regarding the patient; all authors have read and approved the final manuscript.
Supported by A Senior Research Fellowship of Postgraduate Institute of Medical Education and Research, Chandigarh, India
Correspondence to: Safrun Mahmood, PhD, Geneticist, Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India. mahmoodpgi@gmail.com
Telephone: +91-172-2755237 Fax: +91-172-2744401
Received: October 28, 2009
Revised: January 19, 2010
Accepted: January 26, 2010
Published online: July 15, 2010
Abstract

AIM: To investigate p16 gene methylation and its expression in 30 patients with sporadic colorectal adenocarcinoma in a North Indian population.

METHODS: Methylation specific polymerase chain reaction was used to detect p16 gene methylation and immunohistochemistry was used to study the p16 expression in 30 sporadic colorectal tumors as well as adjoining and normal tissue specimens.

RESULTS: Aberrant promoter methylation of p16 gene was detected in 12 (40%) tumor specimens, whereas no promoter methylation was observed in adjoining and normal tissue. Immunohistochemistry showed expression of p16 protein in 26 (86.6%) colorectal tumors whereas complete loss of expression was seen in 4 (13.3%) and reduced expression was observed in 12 (40%) tumors. In the adjoining mucosa, expression of p16 was in 11 (36.6%) whereas no clear positivity for p16 protein was seen in normal tissue. There was a significant difference in the expression of p16 protein in tumor tissue and adjoining mucosa (P < 0.001). The methylation of the p16 gene had a significant effect on the expression of p16 protein (P = 0.021). There was a significant association of methylation of p16 gene with the tumor size (P = 0.015) and of the loss/reduced expression of p16 protein with the proximal site of the tumor (P = 0.047). Promoter methylation and expression of p16 had no relation with the survival of the patients (P > 0.05).

CONCLUSION: Our study demonstrated that promoter hypermethylation of the p16 gene results in loss/reduced expression of p16 protein and this loss/reduced expression may contribute to tumor enlargement.

Keywords: Methylation specific polymerase chain reaction, p16, Methylation, Immunohistochemistry, Colorectal cancer