PT - JOURNAL ARTICLE AU - Di Capua, Daniel M AU - Shanahan, William AU - Bourke, Michele AU - Ramlaul, Navneet AU - Appel, Josh AU - Canney, Aoife AU - Docherty, Neil G AU - McGrath, Erinn AU - Ring, Eabha AU - Jones, Fiona AU - Boyle, Marie AU - McCormack, Janet AU - Gallagher, Tom AU - Hoti, Emir AU - Nolan, Niamh AU - Ryan, John D AU - Houlihan, Diarmaid D AU - Fabre, Aurelie TI - Tumour stemness and poor clinical outcomes in haemochromatosis patients with hepatocellular carcinoma AID - 10.1136/jcp-2022-208679 DP - 2024 Oct 01 TA - Journal of Clinical Pathology PG - 669--675 VI - 77 IP - 10 4099 - http://jcp.bmj.com/content/77/10/669.short 4100 - http://jcp.bmj.com/content/77/10/669.full SO - J Clin Pathol2024 Oct 01; 77 AB - Aims Patients with haemochromatosis (HFE) are known to have an increased risk of developing hepatocellular carcinoma (HCC). Available data are conflicting on whether such patients have poorer prognosis, and there is lack of data regarding the biology of HFE-HCC. We compared the course of HFE-HCC with a matched non-HFE-HCC control group and examined tumour characteristics using immunohistochemistry.Methods In this tertiary care-based retrospective analysis, 12 patients with HFE and 34 patients with alcohol/non-alcoholic steatohepatitis who underwent initially successful curative HCC therapy with ablation or resection were identified from our registry. Time to tumour progression was compared. Resected liver tissue from a separate cohort of 11 matched patients with HFE-HCC and without HFE-HCC was assessed for the expression of progenitor and epithelial–mesenchymal transition markers using immunohistochemistry.Results The median follow-up was 24.39 and 24.28 months for patients with HFE-HCC and those without HFE-HCC, respectively (p>0.05). The mean time to progression was shorter in the HFE group compared with the non-HFE group (12.87 months vs 17.78 months; HR 3.322, p<0.05). Patients with HFE-HCC also progressed to more advanced disease by the end of follow-up (p<0.05). Immunohistochemical analysis of matched HFE-HCC and non-HFE-HCC explants demonstrated increased expression of the cancer stem cell markers EpCAM (epithelial cell adhesion molecule) and EpCAM/SALL4 (spalt-like transcription factor 4) coexpression in HFE-HCC specimens (p<0.05). There was a high frequency of combined tumour subtypes within the HFE cohort.Conclusions This study demonstrates that the clinical course of patients with HFE-HCC is more aggressive and provides the first data indicating that their tumours have increased expression of progenitor markers. These findings suggest patients with HFE-HCC may need to be considered for transplant at an earlier stage.Data are available upon reasonable request.