Immunohistochemical characteristics and potential therapeutic regimens of hepatoid adenocarcinoma of the stomach: a study of 139 cases

Abstract

Hepatoid adenocarcinoma of stomach (HAS) is a special subtype of gastric cancer with poor prognosis. Immunohistochemical analysis could provide important clues for the treatment of HAS. A total of 159 patients were diagnosed as HAS and 139 were enrolled in this study. Statistical differences were determined using relative test methods and survival analyses were performed by the Kaplan–Meier method to find survival differences. All tumors in this study were negative for Epstein–Barr virus‐encoded small RNAs (EBERs) and almost all showed no loss of mismatch repair (MMR) proteins and were positive for alpha fetoprotein (AFP or spalt like transcription factor 4 (SALL4). About half of the tumors had a positive programmed death‐ligand 1 combined positive score (CPS) and 17.3% were positive for human epidermal growth factor receptor 2 (HER2). In addition, there was a relatively high proportion of cmet expression. We also found that HAS patients with recurrent disease treated by emerging therapy had a better survival than those treated with traditional chemotherapy (p = 0.002, median recurrence‐to‐death survival: 23 months versus 6 months); HAS patients who received anti‐HER2 therapy or harbored MMR deficiency had favorable prognosis. Overall, high proportions of MMR protein proficiency, positivity for AFP or SALL4, overexpression of HER2, CPS and cmet, as well as negative EBER findings, are distinctive characteristics of HAS patients. While negative EBER and MMR proficiency indicate molecular features of HAS, positivity for AFP or SALL4 could aid in the diagnosis of HAS. In addition, HAS patients could benefit from anti‐HER2 therapy, immunotherapy, and anti‐angiogenesis therapy.

SALL4 in gastrointestinal tract cancers: upstream and downstream regulatory mechanisms

“…Recently, SALL4 helps to identify clinically and molecularly distinct genomic consensus subtypes (CGSs) (Jeong et al 2023 ). Besides, positivity of SALL4 can aid in the diagnosis of hepatoid adenocarcinoma of stomach (HAS), a special subtype of gastric cancer with poor prognosis (Yang et al 2024 ). Current treatments for GC, including conventional therapy, immunotherapy and targeted therapy, show some curative effects, and clarifying the molecular pathogenesis and regulatory genes underlying GC is necessary for developing novel and personalized treatments for patients.…”