A phenotypical map of disseminated hepatocellular carcinoma suggests clonal constraints in metastatic sites.

Details

Serval ID
serval:BIB_8DA48E6E6627
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A phenotypical map of disseminated hepatocellular carcinoma suggests clonal constraints in metastatic sites.
Journal
Histopathology
Author(s)
Martins-Filho S.N., Alves VAF, Wakamatsu A., Maeda M., Craig A.J., Assato A.K., Villacorta-Martin C., D'Avola D., Labgaa I., Carrilho F.J., Thung S.N., Villanueva A.
ISSN
1365-2559 (Electronic)
ISSN-L
0309-0167
Publication state
Published
Issued date
04/2019
Peer-reviewed
Oui
Volume
74
Number
5
Pages
718-730
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Access to tissue in patients with hepatocellular carcinoma (HCC) is limited compared to other malignancies, particularly at advanced stages. This has precluded a thorough characterisation of molecular drivers of HCC dissemination, particularly in relation to distant metastases. Biomarker assessment is restricted to early stages, and paired primary-metastatic comparisons between samples from the same patient are difficult.
We report the evaluation of 88 patients with HCC who underwent autopsy, including multiregional sampling of primary and metastatic sites totalling 230 nodules analysed. The study included morphological assessment, immunohistochemistry and mutation status of the TERT promoter, the most frequently mutated gene in HCC. We confirm a strong predilection of HCC for lung dissemination, including subclinical micrometastases (unrecognised during imaging and macroscopic examinations) in 30% of patients with disseminated disease. Size of dominant tumour nodule; multinodularity; macrovascular invasion; high histological, nuclear and architectural grades; and cellular crowding were associated with the presence of extrahepatic metastasis. Among the immunohistochemistry markers tested, metastatic nodules had significantly higher K19 and EpCAM expression than primary liver tumours. Morphological and immunohistochemical features showed that metastatic HCC could be traced back to the primary tumour, sometimes to a specific hepatic nodule.
This study suggests limited heterogeneity in metastatic sites compared to primary tumour sites.
Keywords
Aged, Autopsy, Biomarkers, Tumor/analysis, Brazil, Carcinoma, Hepatocellular/genetics, Carcinoma, Hepatocellular/secondary, Cell Differentiation, Cohort Studies, Epithelial Cell Adhesion Molecule/biosynthesis, Female, Fluorescent Antibody Technique, Genetic Heterogeneity, Humans, Liver Neoplasms/genetics, Liver Neoplasms/pathology, Logistic Models, Lung Neoplasms/secondary, Male, Middle Aged, Mutation, Neoplasm Metastasis, Phenotype, Telomerase/genetics, extra-hepatic metastasis, hepatocellular carcinoma, tumor heterogeneity
Pubmed
Web of science
Create date
10/02/2019 16:06
Last modification date
20/08/2019 15:51
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