Abstract
We investigated the prognostic and predictive impact of p53 expression for gastric cancer (GC) patients treated without or with preoperative chemotherapy (CTx) and its relationship with specific molecular GC subtypes. Specimens from 694 GC patients (562 surgical resection specimens without or after CTx, 132 biopsies before CTx) were analyzed by p53 immunohistochemistry. High (H) and low (L) microsatellite instability (MSI) and Epstein–Barr virus positivity were determined previously. Our results show that aberrant p53 expression was a negative prognostic factor in uni- and multivariable analysis in the resection specimens cohort (each p < 0.01). Subgroup analysis showed the strongest prognostic effect for patients with distally located tumors or no CTx treatment. In the biopsy cohort before CTx, p53 did not predict response or survival. p53 expression was significantly different among the molecular subtypes in surgical resection and bioptic specimens with strong association of altered p53 with MSI-L. Patients with MSI-H and aberrant p53 showed the worst survival in the biopsy cohort. In conclusion, the prognostic impact of p53 in GC differs according to tumor localization and CTx. Altered p53 is characteristic for MSI-L, and the p53 status in biopsies before CTx delineates MSI-H subtypes with inverse prognostic impact.
Highlights
With an incidence of about one million new cases in 2018, gastric carcinoma (GC) is the sixth most common cancer worldwide, accounting for about 5.7% of all malignant diseases
Among the 618 patients initially included in the resected cohort, 562 specimens were evaluable for p53 expression
Aberrant p53 expression was significantly associated with worse overall survival (OS) in the overall resected tumor cohort (p log rank = 0.003; hazard ratio (HR), 1.43; 95% confidence interval (CI) 1.13–1.83) (Figure 2A, Table 2)
Summary
With an incidence of about one million new cases in 2018, gastric carcinoma (GC) is the sixth most common cancer worldwide, accounting for about 5.7% of all malignant diseases. The overall survival of patients with GC is limited despite the identification of specific risk factors and improved treatment concepts [1]. This highlights the need for additional molecular characterization, as well as classification, of GC to identify new therapeutic targets in different patient groups. Two of these genetic classification systems that were developed in recent years are the classification according to The Cancer. Several studies showed the negative prognostic relevance of TP53 mutations or aberrant p53 expression in various tumor entities including GC [7,8,9,10]. The prognostic significance of p53 protein expression, especially in the context of perioperative chemotherapy, is controversially discussed, and no prognostic relevance of p53 was observed in some studies [9,11]
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