METHODS: The clinicopathological and molecular characteristics of AFPGC patients (n = 54) were mainly investigated by immunohistochemistry and next-generation sequencing (NGS) approaches.
RESULTS: AFPGC exhibited a higher incidence of lymphatic and vascular invasion than conventional gastric adenocarcinoma (CGA). Despite various morphological patterns, there was mostly no evident difference in clinicopathological characteristics between the GAED and HAC subtypes. Target-enriched NGS profiling of disease mutation landscapes discovered 17 differentially mutated genes between AFPGC and CGA. The AFPGC patients carrying ZNF217 mutations had poorer overall survival than ZNF217 wildtype. Furthermore, ATR showed a significantly higher mutation rate in GAED than in HAC.
CONCLUSIONS: Overall, our study of clinicopathological characters shed light on the differences between CGA and AFPGC, as well as the relationships between the GAED and HAC subtypes of AFPGC. Furthermore, mutation landscape profiling revealed potential diagnostic and prognostic markers for AFPGC and its two subtypes.