BackgroundHepatoid adenocarcinoma of the stomach (HAS) is a highly malignant and rare extrahepatic tumor. The prognosis is controversial because of its rarity and the lack of multi-center cohort studies, especially on the influence of serum Alpha-fetoprotein (AFP) level on prognosis. We aimed to analyze the clinicopathological characteristics and prognosis of HAS, particularly the effect of serum AFP on the prognosis of HAS.MethodsWe retrospectively reviewed clinical data of one HAS patient treated at our institution in 2019 and of 252 patients reported between 1984 and 2020 in research databases.ResultsAmong these patients, 60.1% were > 60 years, 51% had lesions in the gastric antrum, and 51.0% (73/143) had the ulcerative lesion type. The preoperative elevated levels of serum alpha-fetoprotein (AFP) were detected in most patients (76.7%). Lymph-node (84.6%) and preoperative liver metastasis (39.1%) were often found. The high-AFP group was characterized by a higher rate of stage IV (P= 0.000682) and liver metastasis (P= 0.000068). The 1-, 3-and 5-year progression-free survival(PFS) rates were 41%, 18%, and 0%, and the 1-, 3-, and 5-year overall survival (OS) rates were 64%, 26%, and 21%, respectively. The survival analysis showed that OS was significantly shorter for HAS with high-AFP (> 300 ng/ml) than with low-AFP (≤ 300 ng/ml) (P= 0.023). The univariate analysis indicated that the OS of HAS was associated with tumor location, pTNM stage, lymph-node metastasis, surgical resection, and serum AFP > 300 ng/ml. However,the prognostic factors for PFS was only pTNM stage and surgical resection. The multivariate analysis confirmed that the independent prognostic factor affecting OS of HAS included pTNM stage and surgical resection.ConclusionsLiver metastasis was increasingly more likely with increasingly higher serum AFP, but the prognosis of HAS is not necessarily poor. Serum AFP level is an important prognostic indicator in HAS and should be monitored.