Molecular profiling of the biphasic components of hepatic carcinosarcoma by the use of targeted next‐generation sequencing

Abstract

Histopathology 74, 944-958. https://doi.org/10.1111/his.13822 Molecular profiling of the biphasic components of hepatic carcinosarcoma by the use of targeted next-generation sequencing Aims: To better understand the tumourogenesis and molecular features of hepatic carcinosarcoma (HCS). Methods and results: We selected 13 cases of HCS, including the clinicopathological and immunohistochemical features, and analysed the molecular alterations in separately microdissected carcinomatous and sarcomatous components in eight cases by using targeted next-generation sequencing with a panel of 329 cancer-related genes. As a result, transitional areas were observed between the two components of HCS in all cases. Concordance and overlap in genetic alterations were identified in the two histological components of the eight HCS patients, indicating the clonal relatedness of the two tumour components. The most common gene alterations found in both components were TP53 (75%, 6/8) and NF1/2 (38%, 3/8) mutations and VEGFA amplification (25%, 2/8), which may be strongly associated with HCS tumorigenesis. Unique mutations and amplifications found only in one component were also identified. Amplifications involving MET (38%, n = 3/8) and PDGFRA (25%, n = 2/8) were present only in the sarcomatous components, whereas mutation affecting ERBB4 (25%, n = 2/8) and amplifications of CCND1 and FGF3/4/19 (38%, n = 3/8) were present only in the carcinomatous components, indicating their involvement in the clonal evolution of HCS. Furthermore, multiple potential therapeutic targets were identified for HCS. Conclusions: Our findings indicate that HCS could have been of monoclonal origin, and that the diverse clonal evolution might be driven by special molecular alterations in each tumour component. Our results also identify multiple therapeutic targets of HCS, which are valuable for the personalised treatment of HCS.

<p>The Clinicopathological and Imaging Characteristics of Primary Hepatic Carcinosarcoma and a Review of the Literature</p>

“…2 Xin Zhang et al by studying the genes of the components of cancer and sarcoma in 13 patients with HCS found that the changes in the genome were consistent, supporting the idea of the monoclonal origin of HCS. 34 A retrospective analysis was performed on 63 patients with HCS, of which 44 (69.8%) had no history of cirrhosis or hepatic fibrosis, thus supporting the view that hepatocellular sarcoma is a monoclonal tumor.…”

“…Based on the analysis of 63 cases with HCS, the author found that the most common carcinomatous component in HCS is HCC (38/63, 60.3%). Including one case 34 with HCC + CCC, and one with HCC + CCC + Adenocarcinoma + neuroendocrine carcinoma. 6 The most common sarcomatous component is the undifferentiated sarcomatous component which is characterized by spindle cells (24/63, 38.1%).…”

Intrahepatic Carcinosarcoma With Cholangiocarcinoma Elements and Prominent Bile Duct Spread

“…5 To our knowledge, only 6 cases of carcinosarcoma with a cholangiocarcinoma component that meet the AFIP definition have been reported (Table 1). [10][11][12][13][14][15] The sarcomatous components of these cases included chondrosarcoma or osteosarcoma. [10][11][12][13][14][15] The tumor in the present case also included both a carcinoma component (cholangiocarcinoma) and specifically differentiated sarcomatous elements (osteosarcoma and leiomyosarcoma), leading to the diagnosis of intrahepatic carcinosarcoma.…”

“…[10][11][12][13][14][15] The sarcomatous components of these cases included chondrosarcoma or osteosarcoma. [10][11][12][13][14][15] The tumor in the present case also included both a carcinoma component (cholangiocarcinoma) and specifically differentiated sarcomatous elements (osteosarcoma and leiomyosarcoma), leading to the diagnosis of intrahepatic carcinosarcoma. The sarcomatous elements of our case appeared to be derived from the carcinoma because carcinomatous elements transited into atypical spindle cells, which mostly did not exhibit a particular differentiation.…”

“…[3][4][5] However, nearly all intrahepatic cholangiocarcinomas with spindle cell components are sarcomatous intrahepatic cholangiocarcinomas. [6][7][8][9] Accordingly, only a few reports have described carcinosarcomas, [10][11][12][13][14][15] and the characteristic spreading pattern and radiological findings of intrahepatic carcinosarcomas with cholangiocellular differentiation remain unclear.…”