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

Authors
  • Hwang, Hye Jung1
  • Nam, Soo Kyung1
  • Park, Hyunjin2
  • Park, Yujun1
  • Koh, Jiwon3
  • Na, Hee Young1
  • Kwak, Yoonjin3
  • Kim, Woo Ho3
  • Lee, Hye Seung1
  • 1 Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. , (North Korea)
  • 2 Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. , (North Korea)
  • 3 Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea. , (North Korea)
Type
Published Article
Journal
Journal of pathology and translational medicine
Publication Date
Sep 01, 2020
Volume
54
Issue
5
Pages
378–386
Identifiers
DOI: 10.4132/jptm.2020.06.01
PMID: 32601264
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. 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. 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). 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.

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