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

Abstract 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 transplant...

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Published in:The American journal of surgery 2016-08, Vol.212 (2), p.238-245
Main Authors: Vilchez, Valery, M.D, Turcios, Lilia, Ph.D, Zaytseva, Yekaterina, Ph.D, Stewart, Rachel, D.O, Lee, Eun Y., M.D, Maynard, Erin, M.D, Shah, Malay B., M.D, Daily, Michael F., M.D, Tzeng, Ching-Wei D., M.D, Davenport, Daniel, Ph.D, Castellanos, Ana Lia, M.D, Krohmer, Steven, M.D, Hosein, Peter J., M.D, Evers, Bernard Mark, M.D, Gedaly, Roberto, M.D
Format: Article
Language:English
Subjects:
AC133 Antigen - analysis
AC133 Antigen - biosynthesis
alpha-Fetoproteins - analysis
Biomarkers, Tumor - analysis
Biomarkers, Tumor - biosynthesis
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - mortality
Carcinoma, Hepatocellular - surgery
Classification
Female
Hepatitis
Hepatitis C virus
Hepatocellular carcinoma
Humans
Hyaluronan Receptors - analysis
Hyaluronan Receptors - biosynthesis
Immunoglobulins
Laboratories
Liver - chemistry
Liver - metabolism
Liver cancer
Liver cancer stem cells
Liver diseases
Liver Neoplasms - metabolism
Liver Neoplasms - mortality
Liver Neoplasms - surgery
Liver Transplantation
Lymphatic system
Male
Medical imaging
Medical prognosis
Metastasis
Microvessels - pathology
Middle Aged
Neoplasm Invasiveness
Neoplastic Stem Cells - metabolism
Outcomes
Patients
Prognosis
Prognostic factors
Standard deviation
Stem cells
Studies
Surgery
Survival Analysis
Transplants & implants
Tumors
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Summary:Abstract 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.
ISSN:0002-9610
1879-1883
DOI:10.1016/j.amjsurg.2015.12.019