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Prediction of TP53 mutations by p53 immunohistochemistry and their prognostic significance in gastric cancer

Authors
 Hye Jung Hwang  ;  Soo Kyung Nam  ;  Hyunjin Park  ;  Yujun Park  ;  Jiwon Koh  ;  Hee Young Na  ;  Yoonjin Kwak  ;  Woo Ho Kim  ;  Hye Seung Lee 
Citation
 JOURNAL OF PATHOLOGY AND TRANSLATIONAL MEDICINE, Vol.54(5) : 378-386, 2020-09 
Journal Title
 JOURNAL OF PATHOLOGY AND TRANSLATIONAL MEDICINE 
ISSN
 2383-7837 
Issue Date
2020-09
Keywords
Gastric cancer ; Immunohistochemistry ; Next-generation sequencing ; TP53 ; p53
Abstract
Background: Recently, molecular classifications of gastric cancer (GC) have been proposed that include TP53 mutations and their functional activity. We aimed to demonstrate the correlation between p53 immunohistochemistry (IHC) and TP53 mutations as well as their clinicopathological significance in GC. Methods: Deep targeted sequencing was performed using surgical or biopsy specimens from 120 patients with GC. IHC for p53 was performed and interpreted as strong, weak, or negative expression. In 18 cases (15.0%) with discrepant TP53 mutation and p53 IHC results, p53 IHC was repeated. Results: Strong expression of p53 was associated with TP53 missense mutations, negative expression with other types of mutations, and weak expression with wild-type TP53 (p<.001). The sensitivity for each category was 90.9%, 79.0%, and 80.9%, and the specificity was 95.4%, 88.1%, and 92.3%, respectively. The TNM stage at initial diagnosis exhibited a significant correlation with both TP53 mutation type (p=.004) and p53 expression status (p=.029). The Kaplan-Meier survival analysis for 109 stage II and III GC cases showed that patients with TP53 missense mutations had worse overall survival than those in the wild-type and other mutation groups (p=.028). Strong expression of p53 was also associated with worse overall survival in comparison to negative and weak expression (p=.035). Conclusions: Results of IHC of the p53 protein may be used as a simple surrogate marker of TP53 mutations. However, negative expression of p53 and other types of mutations of TP53 should be carefully interpreted because of its lower sensitivity and different prognostic implications.
Files in This Item:
T202006939.pdf Download
DOI
10.4132/jptm.2020.06.01
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Park, Hyunjin(박현진)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182809
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