Genetic and epigenetic analysis of hepatocellular adenomas with atypical morphological features
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Genetic and epigenetic analysis of hepatocellular adenomas with atypical morphological features. / Haefliger, Simon; Hench, Juergen; O'Rourke, Colm J.; Meyer-Schaller, Nathalie; Uzun, Sarp; Saldarriaga, Joan; Weber, Achim; Mazzucchelli, Luca; Jermann, Philip; Frank, Stephan; Andersen, Jesper B.; Terracciano, Luigi; Sempoux, Christine; Matter, Matthias S.
In: Histopathology, Vol. 82, No. 5, 2023, p. 722–730.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Genetic and epigenetic analysis of hepatocellular adenomas with atypical morphological features
AU - Haefliger, Simon
AU - Hench, Juergen
AU - O'Rourke, Colm J.
AU - Meyer-Schaller, Nathalie
AU - Uzun, Sarp
AU - Saldarriaga, Joan
AU - Weber, Achim
AU - Mazzucchelli, Luca
AU - Jermann, Philip
AU - Frank, Stephan
AU - Andersen, Jesper B.
AU - Terracciano, Luigi
AU - Sempoux, Christine
AU - Matter, Matthias S.
PY - 2023
Y1 - 2023
N2 - BackgroundHepatocellular adenoma (HCA) is a rare liver tumour, which can have atypical morphological features such as cytological atypia, pseudoglandular architecture, and altered reticulin framework. Little is known about the genetic and epigenetic alterations of such HCAs and whether they show the alterations classically found in hepatocellular carcinoma (HCC) or in HCA without atypical morphology. MethodsWe analysed five HCAs with atypical morphological features and one HCA with transition to HCC. Every tumour was subtyped by immunohistochemistry, sequenced by a targeted NGS panel, and analysed on a DNA methylation microarray. ResultsSubtyping of the five HCAs with atypical features revealed two beta-catenin mutated HCA (b-HCA), two beta-catenin mutated inflammatory HCA (b-IHCA), and one sonic hedgehog activated HCA (shHCA). None of them showed mutations typically found in HCC, such as, e.g. TERT or TP53 mutations. The epigenomic pattern of HCAs with atypical morphological features clustered with reference data for HCAs without atypical morphological features but not with HCC. Similarly, phyloepigenetic trees using the DNA methylation data reproducibly showed that HCAs with morphological atypia are much more similar to nonmalignant samples than to malignant samples. Finally, atypical HCAs showed no relevant copy number variations (CNV). ConclusionIn our series, mutational, DNA methylation, as well as CNV analyses, supported a relationship of atypical HCAs with nonatypical HCAs rather than with HCC. Therefore, in cases with difficult differential diagnosis between HCC and HCA, it might be advisable to perform targeted sequencing and/or combined methylation/copy number profiling.
AB - BackgroundHepatocellular adenoma (HCA) is a rare liver tumour, which can have atypical morphological features such as cytological atypia, pseudoglandular architecture, and altered reticulin framework. Little is known about the genetic and epigenetic alterations of such HCAs and whether they show the alterations classically found in hepatocellular carcinoma (HCC) or in HCA without atypical morphology. MethodsWe analysed five HCAs with atypical morphological features and one HCA with transition to HCC. Every tumour was subtyped by immunohistochemistry, sequenced by a targeted NGS panel, and analysed on a DNA methylation microarray. ResultsSubtyping of the five HCAs with atypical features revealed two beta-catenin mutated HCA (b-HCA), two beta-catenin mutated inflammatory HCA (b-IHCA), and one sonic hedgehog activated HCA (shHCA). None of them showed mutations typically found in HCC, such as, e.g. TERT or TP53 mutations. The epigenomic pattern of HCAs with atypical morphological features clustered with reference data for HCAs without atypical morphological features but not with HCC. Similarly, phyloepigenetic trees using the DNA methylation data reproducibly showed that HCAs with morphological atypia are much more similar to nonmalignant samples than to malignant samples. Finally, atypical HCAs showed no relevant copy number variations (CNV). ConclusionIn our series, mutational, DNA methylation, as well as CNV analyses, supported a relationship of atypical HCAs with nonatypical HCAs rather than with HCC. Therefore, in cases with difficult differential diagnosis between HCC and HCA, it might be advisable to perform targeted sequencing and/or combined methylation/copy number profiling.
KW - epigenetic
KW - hepatocellular adenoma
KW - hepatocellular carcinoma
KW - liver
KW - methylation analysis
KW - next generation sequencing
KW - MALIGNANT POTENTIAL PROPOSAL
KW - CLASSIFICATION
KW - CARCINOMA
KW - NEOPLASM
U2 - 10.1111/his.14858
DO - 10.1111/his.14858
M3 - Journal article
C2 - 36583256
VL - 82
SP - 722
EP - 730
JO - Histopathology
JF - Histopathology
SN - 0309-0167
IS - 5
ER -
ID: 338303640