title: Ki67, E-cadherin, and p53 as prognostic indicators of long-term outcome after liver transplantation for metastatic neuroendocrine tumors.
abstract: BACKGROUND
  Patients suffering from hepatic metastases of neuroendocrine tumors (NET) are potential candidates for orthotopic liver transplantation. Because recurrence rates are high and outcome is variable, prognostic indicators are required. The aim of our study was to identify predictors of long-term survival with a focus on the impact of tumor biology.
  
  
  METHODS
  We retrospectively analyzed 19 patients who received an orthotopic liver graft for metastatic NET at the Medizinische Hochschule Hannover. Expression of Ki67, E-cadherin, and p53 was studied immunohistochemically in metastases of neuroendocrine tumors of the explanted livers.
  
  
  RESULTS
  Patients were followed up to 146 months after liver transplantation. Six patients died during follow-up. The resulting 1-, 5-, and 10-year survival rates are 89%, 80%, and 50%, respectively. All deaths during long-term follow-up were tumor-associated. Recurrence was diagnosed in 12 patients between 2 weeks and 48 months after liver transplantation. Three patients are without tumor recurrence more than 8 years after liver transplantation. Survival in the 5 patients with low Ki67 and regular E-cadherin staining was significantly better than in the 12 patients with high Ki67 or aberrant E-cadherin expression (7-year survival 100% vs. 0%, respectively, log rank P=0.007). p53 expression did not significantly improve prognostic accuracy.
  
  
  CONCLUSIONS
  We conclude that analysis of Ki67 and E-cadherin expression may improve the identification of patients with a favorable prognosis after liver transplantation for metastatic neuroendocrine tumors.
authors.affiliation: Department of Gastroenterology and Hepatology, Medical School of Hannover, 30171 Hannover, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Rosenau
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Bahr
authors.forename: Reinhard
authors.initials: R
authors.lastname: von Wasielewski
authors.forename: Michael
authors.initials: M
authors.lastname: Mengel
authors.forename: Hartmut H J
authors.initials: HH
authors.lastname: Schmidt
authors.forename: Björn
authors.initials: B
authors.lastname: Nashan
authors.forename: Hauke
authors.initials: H
authors.lastname: Lang
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klempnauer
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Klaus H W
authors.initials: KH
authors.lastname: Boeker
mesh_terms: D000293:Adolescent; D000328:Adult; D015820:Cadherins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary* / Q000601:surgery*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000601:surgery*; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D015820:Cadherins; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53