Hepatocellular adenomas (HCAs) are rare benign
tumors divided into three main subgroups defined by pathomolecular features, HNF1A (H-HCA), mutated β-
catenin (b-HCA), and inflammatory (IHCA). In the case of unclassified HCAs (UHCAs), which are currently identified by default, a high risk of
bleeding remains a clinical issue. The objective of this study was to explore UHCA
proteome with the aim to identify specific
biomarkers. Following dissection of the tumoral (T) and nontumoral (NT) tissue on
formalin-fixed,
paraffin-embedded HCA tissue sections using
laser capture methodology, we performed mass spectrometry analysis to compare T and NT
protein expression levels in H-HCA, IHCA, b-HCA, UHCA, and
focal nodular hyperplasia. Using this methodology, we searched for
proteins which are specifically deregulated in UHCA. We demonstrate that proteomic profiles allow for discriminating known HCA subtypes through identification of classical
biomarkers in each HCA subgroup. We observed specific up-regulation of the
arginine synthesis pathway associated with overexpression of
argininosuccinate synthase (ASS1) and arginosuccinate
lyase in UHCA. ASS1 immunohistochemistry identified all the UHCA, of which 64.7% presented clinical
bleeding manifestations. Interestingly, we demonstrated that the significance of ASS1 was not restricted to UHCA, but also encompassed certain hemorrhagic cases in other HCA subtypes, particularly IHCA.
CONCLUSION: