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

摘要

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 over- expression 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/SSCP- positive cases accounted for remaining 4%cases. CONCLUSION:Our results show that p53 genemutations are significantly correlated with p53 protein overxpression,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.