Subclassification of human hepatic hemangiomas reveals cellular and functional heterogeneity

Background and Aims Despite the high incidence, surgical resection of hepatic hemangioma (HH) is seldomly required and data on HH temporal evolution, biological function and marker expression remain relatively scarce. Limited availability of tissue and a strong bias of resected specimens towards progressive disease has made the development of a disease stage- and phenotype-specific classification difficult, which is currently still missing.

Methods A tissue microarray with 1.5 mm core size consisting of 98 HH, 69 paired tumor-liver interface regions and 66 distant liver tissues was generated. Automatic cell detection, positive cell counts of 11 immunohistochemical markers and vascular morphometry were determined using QuPath. CAT/MRI imaging data of 28 resected patients and RNA-seq data derived from experimental HH were analyzed.

Results HH were characterized by a pronounced inter- and intrapatient heterogeneity regarding macroscopic size, cellular composition, vascular architecture and flow patterns. While highly regressed HH were defined by reduced blood vessel density and flow, cavernous hemangiomas displayed a more pronounced cellular heterogeneity as seen by ERG positive cell counts and EC marker expression (CD31, CD34, THBD). Furthermore, a HH subgroup was identified, which was determined by high cell density and cellular senescence-specific marker expression. Enrichment analysis of experimental HH expression data revealed striking differences of vascular development regulating genes already in early stages of HH development.

Conclusion/Outlook HH may be classified into stage-, morphological- and phenotype-specific subgroups that may identify patients with risk of progressive disease. Current research focuses on the identification of molecular markers that promote disease onset and progression.

Publikationsverlauf

Artikel online veröffentlicht:
26. Januar 2022