OUP user menu

Clinical Significance of Cell Cycle–and Apoptosis-Related Markers in Biliary Tract Cancer
A Tissue Microarray–Based Approach Revealing a Distinctive Immunophenotype for Intrahepatic and Extrahepatic Cholangiocarcinomas

Eva Karamitopoulou MD, Luigi Tornillo MD, Inti Zlobec PhD, Lukas Cioccari MD, Vincenza Carafa PhD, Markus Borner MD, Thomas Schaffner MD, Thomas Brunner PhD, Ioannis Diamantis MD, PhD, Arthur Zimmermann MD, Luigi Terracciano MD
DOI: http://dx.doi.org/10.1309/AJCP35FDCAVANWMM 780-786 First published online: 1 November 2008


Cholangiocarcinoma is the second most common malignant tumor of the liver. We analyzed, immunohistochemically, the significance of cell cycle– and apoptosis-related markers in 128 cholangiocarcinomas (42 intrahepatic, 70 extrahepatic, and 16 gallbladder carcinomas) combined in a tissue microarray. Follow-up was available for 57 patients (44.5%).

In comparison with normal tissue (29 specimens), cholangiocarcinomas expressed significantly more frequently p53, bcl-2, bax, and COX-2 (P < .05). Intrahepatic tumors were significantly more frequently bcl-2+ and p16+, whereas extrahepatic tumors were more often p53+ (P < .05). Loss of p16 expression was associated with reduced survival of patients.

Our data show that p53, bcl-2, bax, and COX-2 have an important role in the pathogenesis of cholangiocarcinomas. The differential expression of p16, bcl-2, and p53 between intrahepatic and extrahepatic tumors demonstrates that there are location-related differences in the phenotype and the genetic profiles of these tumors. Moreover, p16 was identified as an important prognostic marker in cholangiocarcinomas.

Key Words:
  • Cholangiocarcinoma
  • Prognosis
  • Tissue microarray