Expression of CD133 as a tumor stem cell surface marker in hepatocellular carcinoma and its significance in the prognosis of liver transplantation patients

Abstract

Objective To investigate the expression of cluster of differentiation (CD) 133 in hepatocellular carcinoma(HCC) and its significance in the prognosis of patients with HCC undergoing liver transplantation. Methods One hundred and nine HCC tissue samples were collected and analyzed retrospectively from patients undergoing orthotopic liver transplantation for HCC and the pathological diagnosis of HCC was confirmed by histopathology in liver transplantation center of the Third Affiliated Hospital of Sun Yat-sen University from January 2004 to December 2007. Forty-one normal liver tissue samples were collected as control from liver puncture. Clinical pathological data of 109 HCC patients and follow-up data including survival time, tumor recurrence, metastasis and death were collected. Local ethical committee approval had been received and that the informed concent of all participating subjects was obtained. The expression of CD133 was detected by immunohistochemical method in 109 HCC and 41 normal liver tissues, and the relationship between the expression of CD133 and clinicopathological parameters such as ages, sex, alpha-fetoprotein, peripheral blood neurophil to lymphocytes ratio, tumor diameter, tumor number, tumor differentiation degree as well as vascular invasion was analyzed. Results All the patients were followed up and the follow-up period was from 6 to 77 months. Among 109 cases, 37 patients (33.9%) developed tumor recurrence, 24 cases with tumor recurrence in the liver, 6 in the lung, 3 in the abdominal cavity, 4 cases with systemic multiple metastases or bone metastases. Forty patients died during follow-up, among which 35 patients died of tumor recurrence, 3 cases of biliary complications, 1 case of pulmonary infection and 1 case of acute myeloid leukemia. The positive rate of CD133 expression was 40.4%(44/109) in HCC samples, but the expression of CD133 was not detected in normal liver tissue. There was significant difference between two groups(P<0.01). There was relationship between positive expression of CD133 and tumor diameter as well as tumor differentiation grade (all in P<0.05). The 1-, 3-, 5-year survival rates in CD133-positive patients were significantly lower than those in CD133-negative patients (χ2=8.008, P<0.05). Conclusions Expression of CD133 is detected in HCC and HCC patients with positive expression of CD133 show poor prognosis after liver transplantation. Key words: Hepatocellular carcinoma; Liver transplantation; Cluster of differentiation 133 antigen; Stem cell surface marker; Prognosis; Tumor recurrence