Histological and Molecular Findings in Liver Biopsies from Cirrhotic Patients with Hepatocellular Carcinoma

Abstract

Background: Hepatocellular carcinoma (HCC) is a common malignancy in cirrhotic patients, often resulting from chronic liver disease. Understanding the histological and molecular characteristics of HCC in this population is crucial for improving diagnostic accuracy and therapeutic outcomes. Objective: This study aims to investigate the histopathological features and molecular alterations in liver biopsies from cirrhotic patients with HCC, assessing their correlation with tumor progression, prognosis, and potential clinical implications. Methods: A retrospective analysis was conducted on liver biopsy samples from 85 cirrhotic patients diagnosed with HCC. Histological evaluation included fibrosis staging, tumor grading, vascular invasion, and inflammation. Molecular profiling was performed to detect mutations in TP53, CTNNB1, and TERT, as well as epigenetic changes, such as RASSF1A promoter methylation and miRNA dysregulation. Results: The majority of patients (76.5%) had advanced fibrosis (F4). Poorly differentiated tumors and vascular invasion were associated with aggressive disease and lower survival. TP53 mutations were found in 41.2% of patients and correlated with poor differentiation and vascular invasion, while CTNNB1 mutations (23.5%) were linked to well-differentiated tumors. TERT promoter mutations were present in 47.1% of patients, associated with increased tumor aggressiveness. RASSF1A promoter methylation and miR-21 overexpression were also related to worse prognosis. Conclusion: Histological features, coupled with molecular alterations, play a significant role in determining the progression and prognosis of HCC in cirrhotic patients. The integration of molecular markers into diagnostic and therapeutic strategies could provide more personalized treatment options, improving patient outcomes. Further studies are needed to validate these findings and explore new molecular targets for therapy.