Prediction of <i>TP53</i> mutations by p53 immunohistochemistry and their prognostic significance in gastric cancer

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.

Different effects of p53 protein overexpression on the survival of gastric cancer patients according to Lauren histologic classification: a retrospective study

“…For the statistical analysis, p53 IHC staining was interpreted in two tiers: strong nuclear staining in more than 10% of tumor cells was considered as overexpression positive, samples without any nuclear staining of tumor cells (complete absence) or cases exhibiting weak, scattered, or patchy positivity were interpreted as overexpression negative (Fig. 1) [21]. Accuracy of inter/ intra-observer concordance for p53 positivity is very high 1 3 with the following reasons: (1) Most cases were diagnosed by prof. HSL alone, (2) The other cases were diagnosed after sharing the diagnosis criteria with Prof. Lee's.…”

“…Immunostaining of p53 is strongly associated with missense mutation; of the 12 missense mutations, 10 cases (83.3%) were positive for p53 immunostaining, but not with frameshift or nonsense mutations in TP53 [42]. However, according to a recent study of Hwang et al, strong p53 expression could predict nonsynonymous missense mutations with a sensitivity of 90.9%, specificity of 95.4%, and accuracy of 94.2% [21]. Furthermore, p53 overexpression and nonsynonymous TP53 mutations correlate with lower survival compared with other mutations.…”

“…A high level of p53 expression does not necessarily imply a mutation in the gene. However, the overexpression of p53 in most cases (75-85%) is associated with TP53 mutation [19][20][21]. Hence, overexpression of p53 might be considered as an indicator of TP53 mutations [22].…”

The association between the expression of nuclear Yes-associated protein 1 (YAP1) and p53 protein expression profile in breast cancer patients

“…However, some cases but not all cases that had p53 mutant pattern IHC had mutation pattern on IHC was not consistent with all mutations on TP53 sequencing, all wild0type pattern did not have significant TP53 mutation in sequencing (S1 Table ). In addition, there has been studies that correlated the mutation status of TP53 and p53 IHC [26,45]. However, other confirmative method such as Sanger sequencing would have promised more accurate data and results.…”

Expression Pattern and Prognostic Value of p53-Pathway in Gastric Cancer

“…It has been reported that mutations of the p53 gene or other components of p53-pathway (e. g. Mdm2 and Mdmx) are detected in almost all cancer patients [8][9][10][11][12]. Prognostic value of p53 gene expression in gastric cancer has been intensively studied [13,14]. However, some studies suggest that patients with low p53 expression tends to have better survival outcome, while other studies show that p53 expression has no relation with survival outcome [15,16].…”