Background: Tumor suppressor p53 plays a central role in tumor suppression, and mutations in the p53 gene are implicated in tumorigenesis and tumour progression. Although p53 protein expression appears to be correlated to prognosis in several cancers, its prognostic role in gastroesophageal junction adenocarcinoma (AGEJ) remains controversial. We aimed to evaluate the survival outcomes of p53 protein overexpression in AGEJ. Methods: We retrospectively evaluated patients who underwent esophagectomy or total gastrectomy due AGEJ in a Western cohort of patients. p53 expression was analyzed by immunohistochemistry (clone DO-7), and overexpression status was defined when a strong nuclear staining was observed in at least 70% of tumor cells. The overexpressed p53 (overex-p53) cases were compared to the normal p53 group. All patients underwent multimodal treatment, with perioperative chemotherapy. Results: Among the 91 AGEJ, 54 (59.3%) had normal-p53 and 37 (40.7%) overex-p53. There was no significant difference between the groups regarding age (p=0.250), sex (p=0.399), histological grade (p=0.355), tumor pathological response (p=0.771), ypT (p=0.776) and ypN status (p=0.421). Siewert I tumors (p=0.001) and more advanced ypTNM stage (p=0.014) were associated with the overex-p53. In survival analyses, overex-p53 patients had worse disease-free survival than normal-p53 patients (25.9 vs 9.1 months, p=0.003). Similar, overall survival was worse for overex-p53 compared to normal-p53 group (54.6 vs 21.2 months, p=0.002). In multivariate analysis, ASA III/IV, comorbidities, advanced ypT and ypN+, and p53 overexpression were independent factors associated with worse survival. Conclusion: p53 overexpression was associated with poor prognosis, and was an independent factor associated with worse survival in AGEJ.
