Survival outcomes and prognostic factors of gastric carcinoma with neuroendocrine differentiation

Gastric carcinoma (GC) with neuroendocrine differentiation (GCNED) is a rare and particular pathological subtype. The survival outcomes and prognosis of patients with GCNED are currently unclear. We conducted a retrospective cohort study including 309 patients with GC diagnosed between 2012 and 2024 to clarify outcomes after radical resections. Neuroendocrine differentiation was identified using immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule expression. The results showed a GCNED-positivity rate of 22.3% (69/309). The only significant difference in clinicopathological characteristics was the higher perineural invasion (PNI) rate in patients with GCNED-positivity (29% vs. 15.8%, p = .014). Factors such as age, sex, TNM stage, and lymphovascular invasion showed no differences. Regardless of the GCNED-positivity cutoff value (1%, 10%, or 20%), no statistically significant differences in overall survival (OS) or recurrence-free survival (RFS) rates were observed between the two groups. However, in the differentiated histology group, patients with GCNED-positivity showed worse survival rates (p = .015). Logistic regression identified PNI as an independent risk factor for GCNED positivity (odds ratio, 2.08; 95% confidence interval, 1.11-3.91; p = .022). The study showed that while GCNED has a non-negligible prevalence, it has no significant effect on OS or RFS outcomes for patients after radical resections compared to GC without neuroendocrine features. The trend toward a worse prognosis in specific subgroups, such as patients with differentiated GCNED, suggests biological heterogeneity and warrants a longer follow-up to inform stratified therapies.