Cancer stem cell marker expression alone and in combination with microvascular invasion predicts poor prognosis in patients undergoing transplantation for hepatocellular carcinoma

Background The cancer stem cell hypothesis provides an explanation for hepatocellular carcinoma (HCC) heterogeneity. We investigated the expression of CD44 and CD133 alone and in combination with microvascular invasion (MVI) as predictors of prognosis in patients undergoing liver transplantation for HCC. Methods Explanted livers from 95 patients transplanted for HCC were analyzed. Marker expression was evaluated by immunofluorescence. Results Seventy-seven patients were male with a mean age of 56 years. The most common etiologies of cirrhosis were hepatitis C (50%) and alcoholic liver disease (41%). Forty-one patients had laboratory model for end-stage liver disease score greater than 15. Overall survival (OS) at 1-, 3-, and 5-years was 86%, 75%, and 64%, respectively. Recurrence rate was 13% with a median follow-up of 64 months. The 5-year OS was significantly lower in those patients with MVI and CD44 (36.9%) or CD133 (40%). CD44⁺ and CD133⁺ correlated with increased risk of poorly differentiated HCC, and elevated alpha-fetoprotein levels. In combination with MVI, both markers were independently associated with increased recurrence and worse OS (recurrence P <.003, odds ratio = 8.05; P =.001, odds ratio = 9.5, survival P =.001, HR = 3.7; P =.004, HR = 3.2 respectively). Conclusions CD44 or CD133 alone and in combination with MVI are independent predictors of poor prognosis in patients undergoing transplantation for HCC.