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

Journal of Pathology and Translational Medicine 2020년 54권 5호 p.378 ~ 386
황혜정, 남수경, 박현진, 박유준, 고지원, 나희영, 곽윤진, 김우호, 이혜승,
소속 상세정보
황혜정 ( Hwang Hye-Jung ) - Seoul National University College of Medicine Seoul National University Bundang Hospital Department of Pathology
남수경 ( Nam Soo-Kyung ) - Seoul National University College of Medicine Seoul National University Bundang Hospital Department of Pathology
박현진 ( Park Hyun-Jin ) - Yonsei University College of Medicine Gangnam Severance Hospital Department of Pathology
박유준 ( Park Yu-Jun ) - Seoul National University College of Medicine Seoul National University Bundang Hospital Department of Pathology
고지원 ( Koh Ji-Won ) - Seoul National University College of Medicine Seoul National University Hospital Department of Pathology
나희영 ( Na Hee-Young ) - Seoul National University College of Medicine Seoul National University Bundang Hospital Department of Pathology
곽윤진 ( Kwak Yoon-Jin ) - Seoul National University College of Medicine Seoul National University Hospital Department of Pathology
김우호 ( Kim Woo-Ho ) - Seoul National University College of Medicine Seoul National University Hospital Department of Pathology
이혜승 ( Lee Hye-Seung ) - Seoul National University College of Medicine Seoul National University Bundang Hospital Department of Pathology

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.

키워드

Gastric cancer; p53; TP53; Next-generation sequencing; Immunohistochemistry

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