Abstract
ObjectivesHepatoid adenocarcinoma of the stomach (HAS) is characterized by histological resemblance to hepatocellular carcinoma and a poor prognosis. The aim of this study is to elucidate the clinicopathological and molecular characteristics of HAS.MethodsForty-two patients with HAS who received gastrectomy were enrolled in this study. Based on a panel of 483 cancer-related genes, targeted sequencing of 24 HAS and 22 clinical parameter-matched common gastric cancer (CGC) samples was performed. Prognostic factors for overall survival (OS) and disease-free survival (DFS) were analysed with the Kaplan–Meier method.ResultsThe most frequently mutated gene in both HAS and CGC was TP53, with a mutation rate of 30%. Additionally, CEBPA, RPTOR, WISP3, MARK1, and CD3EAP were identified as genes with high-frequency mutations in HAS (10–20%). Copy number gains (CNGs) at 20q11.21-13.12 occurred frequently in HAS, nearly 50% of HAS tumours harboured at least one gene with a CNG at 20q11.21-13.12. This CNG tended to be related to more adverse biobehaviour, including poorer differentiation, greater vascular and nerve invasion, and greater liver metastasis. Pathway enrichment analysis revealed that the HIF-1 signalling pathway and signalling pathways regulating stem cell pluripotency were specifically enriched in HAS. The survival analysis showed that a preoperative serum AFP level ≥ 500 ng/ml was significantly associated with poorer OS (p = 0.007) and tended to be associated with poorer DFS (p = 0.05).ConclusionCNGs at 20q11.21-13.12 happened frequently in HAS and tended to be related to more adverse biobehaviour. The preoperative serum AFP level was a sensitive prognostic biomarker for DFS and OS.
Highlights
Hepatoid adenocarcinoma of the stomach (HAS), a unique subtype of gastric cancer, is gaining increasing attention in recent years due to its aggressive behaviour, especially the potential for liver metastasis and poor prognosis [1,2,3]
Retrospective studies showed that none of the patients with elevated levels of AFP mRNA included in the TCGA dataset can be identified as having hepatoid carcinomas due to the lack of hepatocellular carcinoma (HCC)-like morphology [11,12,13], indicating that the HAS subtype is genetically distinct
Concerning the recurrence patterns, the rate of liver metastasis was as high as 44.4% in the present study population, as expected, whereas only 5.6% of the cases were complicated with peritoneal metastasis
Summary
Hepatoid adenocarcinoma of the stomach (HAS), a unique subtype of gastric cancer, is gaining increasing attention in recent years due to its aggressive behaviour, especially the potential for liver metastasis and poor prognosis [1,2,3]. Previous studies have shown that HAS is the most common of the AFP-producing gastric cancers (GCs), and HAS is commonly believed to have more aggressive biobehaviour and poorer prognosis than cancers without HCC-like morphology [6]. Retrospective studies showed that none of the patients with elevated levels of AFP mRNA included in the TCGA dataset can be identified as having hepatoid carcinomas due to the lack of HCC-like morphology [11,12,13], indicating that the HAS subtype is genetically distinct. Therapeutic targets specific to this unique subgroup have not been identified
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