Correlation of p53 over-expression and alteration in p53 gene detected by polymerase chain reaction-single strand conformation polymorphism in adenocarcinoma of gastric cancer patients from India

Abstract

AIM:To study the alterations in p53 gene among Indian gastric cancer patients and to correlate them with the various clinicopathological parameters. METHODS:A total of 103 gastric cancer patients were included in this study. The p53 alterations were studied by both immunohistochemical method as well as polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. We only studied four (exon 5, 6, 7, and 8) of the 11 p53 exons. The alterations in p53 were also correlated with respect to various clinicopathological parameters. RESULTS:Among 103 cases, p53 over-expression and alteration were detected in 37 (35.92%) and 19 (18.44%) cases, respectively. Most of the p53 alterations were found at exon 5 (31.54%), followed by exon 6 (26.31%), exon 7 (21.04%) and exon 8 (21.04%). A significant correlation of p53 overexpression was found with p53 alteration (P = 0.000). Concordance between p53 alteration (as detected by SSCP) and over-expression [as detected by immunohistochemistry (IHC)] was found in 75% cases. We found that IHC-positive/SSCP-negative cases accounted for 21% of cases and IHC-negative/SSCPpositive cases accounted for remaining 4% cases. CONCLUSION:Our results show that p53 gene mutations are significantly correlated with p53 protein over-expression, with 75% concordance in overexpression and alteration in the p53 gene, but 25% disconcordance also cautions against the assumption that p53 over-expression is always associated with a gene mutation. There may be other mechanisms responsible for stabilization and accumulation of p53 protein with no evidence of gene mutation that reflect an accumulation of a non-mutated protein, or a false negative SSCP result.

Clinicopathological and p53 Gene Alteration Comparison between Young and Older Patients with Gastric Cancer

“…We had shown significant association of p53 expression and alterations with histological grades patients (Karim et al, 2009;Sadeghi et al, 2013). Alteration of p53 gene has been reported controversial with any age group.…”

p53 Codon 72 Polymorphism Interactions with Dietary and Tobacco Related Habits and Risk of Stomach Cancer in Mizoram, India

“…Many studies revealed that tobacco, alcohol, different food habit, infection etc. promote the occurrence of most of the cancers including stomach cancer mutations play an important role (Renault et al, 1993;Tamura et al, 1999;Karim et al, 2009). Several studies have suggested that a mutant allele promotes transformation by inactivating normal p53 function in a dominant-negative fashion (Finlay et al, 1989).…”

Correlation of p53 overexpression with the clinicopathological prognostic factors in gastric adenocarcinoma

“…The estimated newly diagnosed cases were 23,785 in men and 11,819 in women. 1 The etiology of gastric cancer is a complex multistep process characterised by histopathologic precursor lesions and molecular genetic alterations. The p53 is a tumor suppressor gene, located on short arm of chromosome 17p 13.1 and plays a pivotal role in regulating cell growth.…”

“…The p53 is a tumor suppressor gene, located on short arm of chromosome 17p 13.1 and plays a pivotal role in regulating cell growth. [1] p53 mutation is commonly encountered in many human cancers. Frequency of p53 overexpression in gastric adenocarcinoma is 26 to 65%.…”

“…Frequency of p53 overexpression in gastric adenocarcinoma is 26 to 65%. [1] It has also been documented that p53 expression varies with location and histological type of tumor. [3] Overexpression of p53 protein is directly related to enhance proliferative activity [4] and an increased propensity of lymphovascular invasion, lymph node metastasis and advanced TNM stage [5], representing greater tumour aggressiveness.…”