Frequency of p53 Mutations and Epstein-Barr Virus in Pakistani Gastric Cancer Patients and Their Association with the Tumor Grade

Abstract

Gastric carcinoma (GC) is the fourth most common cause of cancer-associated death worldwide. Our study aimed to find the prevalence of TP53 mutations and Epstein-Barr virus (EBV) infection in GC and to investigate their association with the tumor grade. A total of 108 formalin-fixed-paraffin-embedded tissue blocks (98 gastric adenocarcinomas and ten controls) were collected, and DNA was extracted from them. The DNA was used to detect the presence of EBV infection by amplifying the Bam HI W region of the EBV genome in a nested polymerase chain reaction (PCR). Exons 5-7 of TP53 were amplified and sequenced by a commercial sequencer. Immunohistochemistry (IHC) for the expression of caspase-3 was carried out to determine the apoptosis status. Histopathology revealed that of the 98 adenocarcinoma samples, 63.3% (n=62) were poorly differentiated, whereas 36.7% (n=36) were moderately differentiated. Signet rings were present in 30.6% (n=30), and EBV was detected in 18.4% (n=18). Mutation analyses indicated that 76% of the samples were mutated, of which 8% had single nucleotide variations (SNVs) in exon 5 (g.17371G>A and g.17521A>C). Moreover, 76% of the samples had the same SNV (g.18316T>C) in exon 7. We also discovered three novel SNVs; two in exon 5 (g.17371G>A and g.17521A>C) and one in exon 7 (g.18316T>C). No difference in the expression of caspase-3 was observed. The chi-squared test indicated no significant correlation between TP53 mutations with EBV infection and tumor grade. In our cohort, young males had a higher prevalence of GC. The detection of EBV suggests it might be a risk factor for GC in our population.