Multi-omics study of the genomic features and clinical characteristics of hepatic sarcomatoid carcinoma located at different sites

e15153 Background: Hepatic sarcomatoid carcinoma (HSC) is a rare and highly malignant tumor, which accounts for less than 2% of hepatic carcinoma. HSC can occur in the liver (Sarcomatoid hepatocellular carcinoma, SHCC) or in the intrahepatic bile duct (Sarcomatoid intrahepatic cholangiocarcinoma, SiCCA). We aimed to compare the clinical characteristics and genomic features between SHCC and SiCCA. Methods: In this study, we recruited 20 patients who were pathologically diagnosed with HSC from January 2018 to February 2021 in Hunan Provincial People’s Hospital. Whole exome sequencing and PD-L1 expression detected by immunohistochemistry were performed on the qualified tissue samples obtained from18 (14 with SHCC and 4 with SiCCA) of the enrolled patients. Tests were performed in OrigiMed, a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Fisher test was used to determine the association between two categorical variables, and P< 0.05 was considered statistically significant. Results: A total of 15 cases of SHCC and 5 cases of SiCCA were enrolled in this study, with median age of 59 years old (ranged from 34 to 75 years old). Among them, 15 (75%) were diagnosed as AJCC stage III-IV. Compared with SiCCA, we observed a significant higher proportion of undifferentiated samples in SHCC ( P< 0.001) (Table 1). The most commonly mutated genes of HSC included TP53 (64% in SHCC and 75% in SiCCA) and TTN (43% in SHCC and 100% in SiCCA). The most commonly mutated genes in SHCC also included TERT (43%), CCDC168 (36%), and LATS1 (36%), and that in SiCCA also included CDKN2A (50%), KRAS (50%), and CDKN2B (50%). All these genes were mainly enriched in cell cycle and ERBB pathway. In addition, amplifications of HYDIN, C4A, LRRC37A and deletions of CDKN2A, NTRK2, NTRK3, NRG1, PAX3, OR4K5, TPP2 and KRTAP4-6 were detected in the SHCC cohort, and amplifications of ZDHHC11, PMS2 and deletions of NRG1 and CDKN2A were detected in the SiCCA cohort. We also assessed TMB and PD-L1 status among these two cohorts. We found that 86% (12/14) of SHCC and 100% (4/4) of SiCCA had TMB of lower than 10 mutations/Mb. The expression of PD-L1 was positive (CPS > = 1) in 86% (12/14) of SHCC and 75% (3/4) of SiCCA. Conclusions: We are the first to discover the significant differences in tumor differentiation between SHCC and SiCCA. We also profiled the mutational characteristics, TMB status, and PD-L1 status of HSC, shedding light on the precision medicine of HSC. [Table: see text]