Original Article

Modern Pathology (2005) 18, 1498–1503. doi:10.1038/modpathol.3800458; published online 8 July 2005

p53, Ki-67, and serum alpha feto-protein as predictors of hepatocellular carcinoma recurrence in liver transplant patients

Grace Guzman1,4, Victoria Alagiozian-Angelova1, Jennifer E Layden-Almer2, Thomas J Layden2, Guiliano Testa3,4, Enrico Benedetti3, André Kajdacsy-Balla1,4 and Scott J Cotler2

  1. 1Department of Pathology, University of Illinois at Chicago Medical Center (UICMC), College of Medicine, University of Illinois at Chicago, IL, USA
  2. 2Department of Medicine, Division of Hepatology, University of Illinois at Chicago Medical Center (UICMC), College of Medicine, University of Illinois at Chicago, IL, USA
  3. 3Department of Surgery, Division of Transplantation, University of Illinois at Chicago Medical Center (UICMC), College of Medicine, University of Illinois at Chicago, IL, USA
  4. 4The Cancer Center, University of Illinois at Chicago Medical Center (UICMC), College of Medicine, University of Illinois at Chicago, IL, USA

Correspondence: Dr G Guzman, MD, Department of Pathology, Room 446, College of Medicine West, University of Illinois at Chicago, 1819 W, Polk Street, M/C 847, Chicago, IL 60612, USA. E-mail: graceguz@uic.edu

Received 13 April 2005; Revised 27 May 2005; Accepted 28 May 2005; Published online 8 July 2005.

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Abstract

Patients with hepatocellular carcinoma who undergo orthotopic liver transplantation (OLT) are at risk for post-transplant tumor recurrence. The aim of this study was to evaluate whether expression of p53 and Ki-67 in hepatocellular carcinoma lesions present in explanted liver tissue was associated with time to tumor recurrence after OLT. Subjects consisted of 20 consecutive patients who underwent OLT and were found to have hepatocellular carcinoma in the liver explant. Immunostaining for p53 and Ki-67 was performed by standard methods. The presence of nuclear immunostaining in >10% of the tumor tissue was considered positive. Time to recurrence of hepatocellular carcinoma after OLT was compared between patients with positive and negative immunostaining by the log rank test. Multivariate analysis was performed using a Cox regression model to control for potentially confounding clinical factors. Time to post-transplant hepatocellular carcinoma recurrence was significantly more rapid in p53+ (P=0.0007) and Ki-67+ cases (P=0.001). These associations remained significant in multivariate analysis. Furthermore, time to recurrent hepatocellular carcinoma was significantly shorter in patients with a serum alpha feto-protein (AFP) level greater than or equal to100 ng/ml at time of diagnosis, compared to those with an AFP level <100 ng/ml (P=0.003). In conclusion, expression of p53 and Ki-67 in hepatocellular carcinoma lesions, and a serum AFP level greater than or equal to100 ng/ml were associated with more rapid recurrence of hepatocellular carcinoma after OLT. Identification of patients at risk for early post-transplant recurrence could be used to guide surveillance and adjuvant treatment strategies.

Keywords:

immunohistochemistry, recurrent hepatocellular carcinoma

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