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Updated: Dec 21, 2025

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
Morphophenotypic Classification of Hepatocellular Carcinoma: the Biliary/Stem Cell Subgroup and Worst
Rui Caetano Oliveira1,2,3, Ricardo Martins4,5,6,7,8, Ana Margarida Abrantes4,5
1Serviço de Anatomia Patológica, Pathology Department, Centro Hospitalar e Universitário de Coimbra, Piso-3, Praceta Mota Pinto, 3000-075, Coimbra, Portugal. ruipedrocoliveira@hotmail.com.
Background:
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the third cause of cancer-related death. Current clinical/pathological criteria contribute to risk stratification, but are far from the desired on individualized medicine. Recently, HCC classifications have been published based on immunohistochemical and morphological features.
Methods:
A retrospective review of patients submitted to surgical treatment-partial hepatectomy (PH) or liver transplantation (LT), with pathological diagnosis of HCC, in a 9-year period (2007-2015) was performed.
Results:
Applying the classification of Srivastava et al. (#1), based on the expression of CD31, p53, AFP and CD44, tumour size and presence of vascular invasion, HCC were categorized as low- and high-risk HCC. With the classification of Tsujikawa et al. (#2), HCC were classified into biliary/stem cell marker positive, Wnt signalling positive and the "all negative" HCC, according to the expression of CK19, SALL4, β-catenin glutamine synthetase, EpCAM and p53. There were sixty-six patients (53 males; 13 females), with median age of 64.5 ± 9.46 years (range 38-86), with solitary HCC, comprehending 37 PH (56.1%) and 29 LT (43.9%). The mean overall survival (OS) was 75.4 ± 6.9 months. Biliary/stem cell type of HCC was a predictive factor of worse OS on the overall population (24.4 versus 78.3 months, p = 0.032) and in PH cohort (11.5 versus 64.01 months, p = 0.016), on uni- and multivariate analyses.
Conclusion:
These results support the relevance of a risk stratification classification of HCC. Classification #2 seems adequate to our reality demonstrating OS impact, allowing its application in future biopsies, prompting individualized medicine.

