Aberrant expression of p53 in gastric carcinoma and its association with HER2 status

Abstract

Introduction. p53 is a tumor suppressor, whose expression is actively studied in many tumors. However, scientists argue about aberrant p53 expression criteria and whether tumoral p53 expression correlates with various clinical and morphological parameters of gastric cancer and has a prognostic role. No data were published in Russia on the incidence of tumors with p53 overexpression. It remains unclear whether aberrant p53 expression is an independent prognostic sign in gastric cancer. The study aimed to evaluate the frequency of p53 expression in gastric adenocarcinomas in the Russian population, to give the definition for aberrant p53 expression, and to clarify the relationship between p53 expression, clinical and morphological tumor characteristics, HER2 status, and the impact of p53 expression on the prognosis. Materials and methods. We studied surgical pathology samples from 310 patients with verified gastric cancer. The age of the patients ranged from 22 to 85 years (mean 63 years). Each sample was stained immunohistochemically with antibodies to p53 (clone DO-7) and the HercepTest kit (Dako/Agilent Technologies). We compared the results with the main clinical and morphological characteristics of gastric cancer and patient survival data. Results.The frequency of aberrant p53 expression was 49.4%. Aberrant expression should include both cases with overexpression and cases with a complete absence of marker expression. In contrast to the normal p53 expression group, the group with aberrant p53 expression was characterized by more frequent proximal tumor location; fewer diffuse and infiltrative carcinoma forms; a significant predominance of tubular, papillary, and mixed histological types (p=0.000); significantly higher degrees of differentiation (p=0.011); a significantly lower number of cases with identified signet ring cells in tumors (p=0.000); a lower frequency of stage IV in patients; and a significant predominance of the intestinal and intermediate subtype according to P. Lauren classification (p=0.000). The overall five-year survival in patients with aberrant p53 expression was not significantly lower (p=0.392) than in patients with normal p53 expression (35.6%, median 36 months and 42.5%, median 51 months, respectively). According to the Cox proportional hazards regression model, the p53 expression level is not a significant prognostic sign (HR=1.281; CI: 0.818–2.008, p=0.280). In the group with aberrant p53 expression, a positive HER2 status was detected significantly more often (13.7%) than in the group with normal p53 expression (1.9%, p=0.000). Conclusion. The group with aberrant p53 expression can be considered as an immunohistochemical analog of the chromosomally unstable gastric cancer subtype (according to TCGA) and the MSS/TP53- subtype (according to ACRG). In the group with aberrant p53 expression, cases with a positive HER2 status were significantly more common. Keywords: р53, HER2/neu, ERBB2, gastric cancer, gastric adenocarcinoma, immunohistochemistry