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

Valery Vilchez, Lilia Turcios, Yekaterina Zaytseva, Rachel Stewart, Eun Y. Lee, Erin Maynard, Malay B. Shah, Michael F. Daily, Ching Wei D Tzeng, Daniel Davenport, Ana Lia Castellanos, Steven Krohmer, Peter J. Hosein, Bernard Mark Evers, Roberto Gedaly

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
JournalAmerican Journal of Surgery
DOIs
StateAccepted/In press - Jun 18 2015
Externally publishedYes

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Neoplastic Stem Cells
Hepatocellular Carcinoma
Transplantation
Survival
Recurrence
Odds Ratio
Alcoholic Liver Diseases
End Stage Liver Disease
alpha-Fetoproteins
Hepatitis C
Liver Transplantation
Fluorescent Antibody Technique
Fibrosis
Liver

Keywords

  • Hepatocellular carcinoma
  • Liver cancer stem cells
  • Liver transplantation
  • Outcomes
  • Prognostic factors

ASJC Scopus subject areas

  • Surgery

Cite this

Cancer stem cell marker expression alone and in combination with microvascular invasion predicts poor prognosis in patients undergoing transplantation for hepatocellular carcinoma. / Vilchez, Valery; Turcios, Lilia; Zaytseva, Yekaterina; Stewart, Rachel; Lee, Eun Y.; Maynard, Erin; Shah, Malay B.; Daily, Michael F.; Tzeng, Ching Wei D; Davenport, Daniel; Castellanos, Ana Lia; Krohmer, Steven; Hosein, Peter J.; Evers, Bernard Mark; Gedaly, Roberto.

In: American Journal of Surgery, 18.06.2015.

Research output: Contribution to journalArticle

Vilchez, V, Turcios, L, Zaytseva, Y, Stewart, R, Lee, EY, Maynard, E, Shah, MB, Daily, MF, Tzeng, CWD, Davenport, D, Castellanos, AL, Krohmer, S, Hosein, PJ, Evers, BM & Gedaly, R 2015, 'Cancer stem cell marker expression alone and in combination with microvascular invasion predicts poor prognosis in patients undergoing transplantation for hepatocellular carcinoma', American Journal of Surgery. https://doi.org/10.1016/j.amjsurg.2015.12.019
Vilchez, Valery ; Turcios, Lilia ; Zaytseva, Yekaterina ; Stewart, Rachel ; Lee, Eun Y. ; Maynard, Erin ; Shah, Malay B. ; Daily, Michael F. ; Tzeng, Ching Wei D ; Davenport, Daniel ; Castellanos, Ana Lia ; Krohmer, Steven ; Hosein, Peter J. ; Evers, Bernard Mark ; Gedaly, Roberto. / Cancer stem cell marker expression alone and in combination with microvascular invasion predicts poor prognosis in patients undergoing transplantation for hepatocellular carcinoma. In: American Journal of Surgery. 2015.
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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.",
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T1 - Cancer stem cell marker expression alone and in combination with microvascular invasion predicts poor prognosis in patients undergoing transplantation for hepatocellular carcinoma

AU - Vilchez, Valery

AU - Turcios, Lilia

AU - Zaytseva, Yekaterina

AU - Stewart, Rachel

AU - Lee, Eun Y.

AU - Maynard, Erin

AU - Shah, Malay B.

AU - Daily, Michael F.

AU - Tzeng, Ching Wei D

AU - Davenport, Daniel

AU - Castellanos, Ana Lia

AU - Krohmer, Steven

AU - Hosein, Peter J.

AU - Evers, Bernard Mark

AU - Gedaly, Roberto

PY - 2015/6/18

Y1 - 2015/6/18

N2 - 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.

AB - 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.

KW - Hepatocellular carcinoma

KW - Liver cancer stem cells

KW - Liver transplantation

KW - Outcomes

KW - Prognostic factors

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