Premium
A phenotypical map of disseminated hepatocellular carcinoma suggests clonal constraints in metastatic sites
Author(s) -
MartinsFilho Sebastiao N,
Alves Venancio A F,
Wakamatsu Alda,
Maeda Miho,
Craig Amanda J,
Assato Aline K,
VillacortaMartin Carlos,
D'Avola Delia,
Labgaa Ismail,
Carrilho Flair J,
Thung Swan N,
Villanueva Augusto
Publication year - 2019
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13809
Subject(s) - hepatocellular carcinoma , phenotype , pathology , carcinoma , biology , medicine , cancer research , genetics , gene
Aims 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. Methods and results 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 Ep CAM 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. Conclusions This study suggests limited heterogeneity in metastatic sites compared to primary tumour sites.