Sarcomatoid hepatocellular carcinoma is distinct from ordinary hepatocellular carcinoma: Clinicopathologic, transcriptomic and immunologic analyses

Abstract

Sarcomatoid hepatocellular carcinoma (SHCC), which was a rare histological subtype of hepatocellular carcinoma (HCC), is currently subclassified as poorly differentiated HCC because of insufficient evidence to define SHCC as a subtype of HCC. We aimed to assess the feasibility of classifying SHCC as a histological subtype of HCC by comprehensively identifying novel and distinct characteristics of SHCC compared to ordinary HCC (OHCC). Fifteen SHCCs (1.4%) defined as HCC with at least a 10% sarcomatous component, 15 randomly disease-stage-matched OHCCs and 163 consecutive OHCCs were extracted from 1106 HCCs in the Pathology Database (1997-2019) of our hospital. SHCC patients showed poor prognosis, and the tumors could be histologically subclassified into the pleomorphic, spindle and giant cell types according to the subtype of carcinomas with sarcomatoid or undifferentiated morphology in other organs. The transcriptomic analysis revealed distinct characteristics of SHCC featuring the upregulation of genes associated with epithelial-to-mesenchymal transition and inflammatory responses. The fluorescent multiplex immunohistochemistry results revealed

Sarcomatoid hepatocellular carcinoma: From clinical features to cancer genome

“…Kodama T et al identified cancer‐related genes such as MET , GAB1 , and HECT that may drive epithelial‐mesenchymal transition in HCC 17 . Morisue R et al detected the transcriptome in two sarcomatoid HCCs and five non‐sarcomatoid HCC and found upregulation of genes that associated with epithelial‐to‐mesenchymal transition and inflammatory responses in sarcomatoid HCC 18 . In our study, we found distinct genetic patterns between sarcomatoid HCC and non‐sarcomatoid HCC.…”

“…17 Morisue R et al detected the transcriptome in two sarcomatoid HCCs and five non-sarcomatoid HCC and found upregulation of genes that associated with epithelial-to-mesenchymal transition and inflammatory responses in sarcomatoid HCC. 18 In our study, we found distinct genetic patterns between sarcomatoid HCC and non-sarcomatoid HCC. The major finding was that sarcomatoid HCC had a high rate of rearrangement and homozygous deletion in CDKN2A gene, which leads to a loss of gene function.…”

Primary Liver Sarcomatoid Carcinoma: A Case Series and Literature Review

“…Recently, features of immune infiltration were revealed for the first time, which contained pathological tissues from 31 cases, that PD-L1 expression of SHC was significantly higher than that of HCC, which also associated with poor prognosis in DFS (HR= 5.036, 95% CI 1.382–18.354) and OS (HR=5.696, 95% CI 1.473–22.081). 47 , 50 It suggests that individualized analysis of immune check point and immunotherapy might be beneficial in PLSC patients, but adverse events still have to be carefully monitored.…”

Disease Control Achieved Using Atezolizumab + Bevacizumab in a Patient With Sarcomatoid Hepatocellular Carcinoma (SHCC), a Rare Variant Excluded From the IMbrave150 Trial

“… 5 Studies consistently show that SHCC is associated with worse outcomes and is considered an independent unfavorable prognostic indicator. 11 , 18 …”