Clinicopathological features and prognosis of patients with resectable HAS/GAED: A multicenter nested case-control study from China.

[BACKGROUND] Hepatoid adenocarcinoma of the stomach (HAS) and gastric adenocarcinoma with enteroblastic differentiation (GAED) are rare and highly aggressive subtypes of gastric cancer (GC).

[AIMS] This study aimed to investigate the clinicopathological characteristics and prognostic outcomes of patients with HAS and GAED.

[METHODS] This multicenter retrospective study compared 107 patients with HAS/GAED with 428 patients with conventional GC (cGC) after 4:1 propensity score matching (PSM). The primary outcomes included disease-free survival (DFS), gastric cancer-specific survival (GCSS), and overall survival (OS). Survival analyses were performed using Cox proportional hazards models and Kaplan-Meier curves.

[RESULTS] With a median follow-up of 33 months, patients in the HAS/GAED group, compared with those in the cGC group, exhibited larger tumor size, poorer histological differentiation, higher preoperative carcinoembryonic antigen (CEA) levels, and a higher rate of human epidermal growth factor receptor 2 (HER2) overexpression (all P<0.05). Multivariate analysis identified elevated CEA levels, perineural invasion (PNI), and pathological N (pN) category as independent risk factors for poor prognosis, whereas postoperative chemotherapy was identified as a protective factor. The HAS/GAED group demonstrated significantly worse DFS (P<0.001), GCSS (P=0.001), and OS (P=0.028) compared with the cGC group. No significant prognostic differences were observed between patients with HAS and those with GAED.

[CONCLUSION] HAS and GAED are highly aggressive subtypes of GC, characterized by distinct clinicopathological features and an unfavorable prognosis.