Z Gastroenterol 2009; 47 - P353
DOI: 10.1055/s-0029-1241601

Inhibition of differentiaton protein expression in advanced Biliary Tract Cancer

J Harder 1, 2, M Müller 1, J Hasskarl 3, V Gumpp 2, HE Blum 1, A Schmitt-Graeff 4, OG Opitz 2
  • 1Universität Freiburg, Medizinische Universitätsklinik, Medizin II, Freiburg, Germany
  • 2Universität Freiburg, Tumorzentrum Ludwig Heilmeyer – Comprehensive Cancer Center Freiburg, Freiburg, Germany
  • 3Universität Freiburg, Medizinische Universitätsklinik, Medizin I, Freiburg, Germany
  • 4Universität Freiburg, Pathologisches Institut, Freiburg, Germany

Purpose: Inhibition of differentiation (ID) proteins are helix-loop-helix transcription factors, which are involved in the carcinogenesis of various tumors. For ID protein expression there are no data on biliary tract cancer (BTC) so far.

Methods: We analyzed the expression of ID proteins 1–4 in 120 patients with advanced BTC and in 9 controls by immunohistochemistry (IHC). The expression data were correlated with clinicopathological variables in order to determine the relevance of the ID proteins in BTC. The IHC results were categorized into four groups for cytoplasmic (negative, weak, moderate, strong) and for nuclear staining (0–10%; 11–50%, 51–80% and 81–100% of 100 counted cells), respectively.

Results: The study cohort comprised 58 (48.3%) women and 62 (51.7%) men with a mean age of 63.5 years (range 32–84). In 39 patients the cholangiocarcinoma was extrahepatic (EHCC), in 48 patients intrahepatic (IHCC) and 33 patients had gallbladder cancer (GBCC). Patients with EHCC had a significantly better overall survival (OS) than patients with IHCC or GBCC (p=0.002). Healthy controls showed only a weak expression of ID proteins 1–3 expression while a significant overexpression of ID proteins 1–3 could be demonstrated in 68.2% (nuclear ID1), 77.5% (cytoplasmic ID2) and 68.3% (nuclear ID3) of BTC. There was no correlation between the expression of ID protein 1–4, tumor grading or BTC subtype. In patients who were not treated by chemotherapy (n=56) there was a significant correlation between nuclear ID protein 1 overexpression and a reduced OS (p=0.001) while for the whole study population it was borderline statistically significant (p=0.057). In the group of patients who received chemotherapy (n=64) absent nuclear ID protein 2 expression was associated with a longer OS (p=0.001).

Conclusions: ID proteins 1–3 were significantly overexpressed in advanced BTC. Further, the overexpression of ID protein 1 is prognostic for shorter OS in patients not treated by chemotherapy. In patients treated by chemotherapy absent nuclear 2 expression is a strong prognotic marker for better OS. These data suggest that ID proteins play a role in the carcinogenesis of BTC. The usefulness of ID proteins as prognostic biomarkers should now to be evaluated prospectively.