Mutant p53 and TP53 mutations in esophageal squamous cell carcinoma: consistency and diagnostic significance.

Background and objective: TP53 mutation is an initiating event in tumorigenesis in many cancers. Mutant p53 expression is an important manifestation of TP53 mutations, however, this association has not yet been confirmed in esophageal squamous cell carcinoma (ESCC). This study comprised three components. The first was screening for TP53 mutations using whole-exome sequencing (WES) or whole-genome sequencing (WGS). The second was identifying mutant p53 expression by immunohistochemical (IHC) staining to explore the association between mutant p53 expression and TP53 mutations. The third was assessing the diagnostic value of mutant p53 expression in patients with ESCC. Methods: Eighteen fresh ESCC specimens were collected for WES. For cases without TP53 mutations detected by WES, WGS was performed to confirm the results and identify additional mutations. These samples underwent p53 IHC staining, and p53 expression was assessed independently by two senior pathologists. The Kappa coefficient was used to evaluate interobserver consistency. An additional 60 ESCC samples and corresponding adjacent tissues were collected for IHC staining. The chi-square test was used to assess the diagnostic value of p53 expression. Results: WES revealed TP53 mutations in 13/18 cases. WGS of the five WES-negative samples identified TP53 mutations in four of them. Overall, TP53 mutations were detected in 17/18 cases (94.44%). Mutant p53 expression was present in all ESCC cases, and the consistency rate between TP53 mutation and p53 protein expression was 94.44% (17/18). In the combined WES + WGS cohort, mutant p53 expression was detected in 18/18 (100.00%) patients with ESCC. In the IHC cohort, mutant p53 expression was detected in 60/60 (100.00%) patients with ESCC. In both cohorts, Type I mutant p53 expression was the most common subtype, followed by Type IV. Type IV mutant expression was not observed in the WES + WGS cohort. The Kappa value for the two pathologists to was 0.954 (0.911-1.000). The sensitivity and specificity of mutant p53 expression for diagnosing ESCC were 1.00 (0.95-1.00) and 1.00 (0.95-1.00), respectively. Conclusion: Mutant p53 expression can serve as an alternative marker for TP53 mutation screening used WES or WGS. Mutant p53 expression shows high sensitivity and specificity in distinguishing ESCC and can assist in differentiating benign from malignant esophageal lesions. Five mutant p53 expression subtypes were identified in this study; however, their clinical significance requires further investigation.