Molecular characterization of hepatic epithelioid hemangioendothelioma reveals alterations in various genes involved in DNA repair, epigenetic regulation, signaling pathways, and cell cycle control

Abstract

Epithelioid hemangioendotheliomas (EHE) of the liver are rare, low‐malignant vascular tumors whose molecular pathogenesis is incompletely understood. The diagnosis of EHE is challenging, and the course of the disease can be highly variable. Therapeutic options for EHE are limited, including resection of primary and metastatic tumors, organ transplantation and rather ineffective systemic approaches. Driver mutations have been reported (fusion transcripts of either YAP‐TFE3 or WWTR1‐CAMTA1) but comprehensive molecular profiling has not been performed. Our aim was to molecularly characterize hepatic EHE to identify new molecular targets. Eight primary hepatic EHE were analyzed by next‐generation sequencing using a 409‐gene panel. The majority of primary hepatic EHE revealed a low number of mutations. Genes that were mutated primarily are involved in DNA repair, epigenetic regulation, signaling pathways and cell cycle control, indicating that EHE present with mutations in various functions. Although only detecting a low mutation rate, a comparison with comprehensive databases (target db V3) revealed mutations in five genes with putative therapeutical options. Therefore, our findings help to shed light on the molecular background of EHE and might pave the way to new therapeutic approaches.

Successful chemotherapy with continuous immunotherapy for primary pulmonary endovascular epithelioid hemangioendothelioma: A case report

“…New biomarkers of TP53, murine double minute-2 and decreased caveolin-1 would be verified in the development of EHE. [11] Recently multi-mutation in functions like DNA repair, epigenetic modification and cell cycle dysregulation influence the pathogenesis, [12] just as the mutation of MSH2 in this case, which represents a regulator of mismatch DNA repair. It revealed that MSH2 might influence the pathogenesis of PE-EHE.…”

Three cases of hepatic epithelioid hemangioendothelioma evaluated using conventional and contrast‐enhanced ultrasound: Case reports

“…Initial observations to assess disease behavior may better stratify treatment options, and surgical treatment should be reserved for candidates who must undergo hepatectomy or transplantation 1,26 . Furthermore, the correct diagnosis of HEHE and its differentiation from other tumors are vital importance for prognosis and treatment 27 . Understanding the imaging features of this rare tumor may help in the detection and timing of further surgical treatment of this potentially curable disease.…”