Abstract 4746: Genomic alterations and clinical correlations of Chinese hepatoid adenocarcinoma patients
Authors: Liu Tianshu , Chen Erbao , Xu Chen , Li Wei , Liu Mengling , Wei Yichou , Yu Yiyi , Cui Yuehong , Li Qian , Zhang Shuirong , Huang Lujia , Qu Yueting 
Published: September 2020

Abstract
Background: In recent years, hepatoid adenocarcinoma (HAC), a rare tumor subtype, has attracted more and more attention because of its malignant nature, especially its poor prognosis due to frequent liver metastasis. HAC, recognized as an extrahepatic cancer that resembles hepatocellular carcinoma (HCC), is characterized by the solid sheet-like growth structures of hepatoid differentiation and excessive production of alpha-fetoprotein (AFP). Hepatoid adenocarcinoma of the stomach (HAS) is the most common site of HAC, however, the differences between HAS and HAC of other organs are unknown.
Methods: Our Chinese HAC cohort consisted of 31 samples (25 HAS patients and 6 HAC of other organs patients) that were collected in the form of formalin-fixed, paraffin-embedded (FFPE) tumor tissues at Zhongshan Hospital from July 2013 to August 2017 for whole exome sequencing (WES) (OrigiMed, Shanghai).
Results: A total of 31 patients with HAC had surgical treatment, 25 patients with HAS (median age 66.5 years, range 48-82) and 6 patients with HAC of other organs (median age 62.5 years, range 52-67). Most HAS patients were male (18/25, 72%), and most HAC of other organs patients were female (4/6, 66.7%). Survival analysis revealed that compared with patients with HAS, patients with HAC of other organs had a significantly poorer overall survival (OS) (p=0.0081) and disease-free survival (DFS) (p=0.0011). The most frequently mutated genes in the HAS tumor samples were TP53 (42%), MUC19 (35%), and TTN (35%). The substitution mutations of CDK4, KRT34 and GOLGA6L3 were only found in HAC from other organs samples but not from HAS samples. Copy number variations (CNVs) of CCNE1, VSTM2B, PLEKHF1 and POP4 were only identified in HAS samples. Interestingly, these 4 genes were located at chr19 and were co-mutated in 5 patients who had a significantly poorer OS than those without these CNVs (11.1 months vs. 19.3 months, respectively, p=0.045). The tumor mutational burden (TMB) of HAS was significantly higher compared with HAC of other organs was also significantly different (4 muts/Mb vs. 1.2 muts/Mb, respectively, p=0.012).
Conclusions: Our study revealed the genomic profiling of Chinese HAC patients. Compared to patients with HAS, patients with HAC of other organs had a significantly poorer OS and DFS. The origin for HAC was associated with specific gene mutations and the TMB value. Patients with CNVs in chr19 were significantly associated with a poorer OS.
Citation Format: Tianshu Liu, Erbao Chen, Chen Xu, Wei Li, Mengling Liu, Yichou Wei, Yiyi Yu, Yuehong Cui, Qian Li, Shuirong Zhang, Lujia Huang, Yueting Qu. Genomic alterations and clinical correlations of Chinese hepatoid adenocarcinoma patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4746.