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.
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.
Karamitopoulou
Eva
E
Institutes of Pathology, University of Basel, Basel, Switzerland Second Department of Pathology, University of Athens, Haidari, Athens, Greece.
Tornillo
Luigi
L
Zlobec
Inti
I
Cioccari
Lukas
L
Carafa
Vincenza
V
Borner
Markus
M
Schaffner
Thomas
T
Brunner
Thomas
T
Diamantis
Ioannis
I
Zimmermann
Arthur
A
Terracciano
Luigi
L
D017209:Apoptosis / Q000502:physiology*; D017734:Bile Ducts, Extrahepatic / Q000378:metabolism; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism; D001661:Biliary Tract Neoplasms / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005706:Gallbladder Neoplasms / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D040081:Protein Array Analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051546:Cyclooxygenase 2