Z Gastroenterol 2005; 43 - P383
DOI: 10.1055/s-2005-920166

The peripheral benzodiazepine receptor: Clinical importance of up-regulation during human colorectal carcinogenesis and tumor spread

P Grabowski 1, K Maaser 2, Y Oezdem 3, A Krahn 4, B Heine 5, H Stein 6, HJ Buhr 7, M Zeitz 8, H Scherübl 9
  • 1Charité-CBF, Medizinische Klnik I Gastroenterologie/Infektiologie/Rheumatologie, Berlin
  • 2Charité-CBF, Med. Klinik I, Gastroenterologie, Berlin
  • 3Charité-CBF, Med. Klinik I, Gastroenterologie, Berlin
  • 4Charité-CBF, Med. Klinik I, Gastroenterologie, Berlin
  • 5Charité-CBF, Institut für Pathologie, Berlin
  • 6Charité-CBF, Institut für Pathologie, Berlin
  • 7Charité-CBF, Chirurgische Klinik, Berlin
  • 8Med. Klinik I Gastroenterologie Charite Campus Benjamin Frankin, Berlin
  • 9Charité-CBF, Med. Klinik I, Gastroenterologie, Berlin

Aims: The peripheral benzodiazepine receptor (PBR) is overexpressed in a variety of cancers. In UICC III colorectal cancers, a high level of PBR overexpression correlates with poor prognosis. However, little is known about the role of PBR in the development and progression of colorectal cancer. This study addresses the up-regulation of PBR during colorectal carcinogenesis and tumor spread.

Methods: 116 consecutive patients undergoing surgery for colorectal cancer with either regional (59 patients) or distant metastases (57 patients) were followed-up for five years or until death. 24 of the 59 patients with initial UICC III cancers later developed distant metastases. PBR overexpression in tumor specimens was determined by immuno-histochemistry.

Results: UICC III patients with colorectal primaries highly overexpressing PBR developed metastases significantly more often than patients with low PBR overexpression in their primary carcinoma. In 54 of the 116 patients adenomas and/or metastases and/or recurrences were available to be studied for PBR up-regulation during colorectal carcinogenesis and tumor spread. PBR was found to be overexpressed in 86% of early and late adenomas. Furthermore, 85% of primaries and of 86% of metastases displayed PBR overexpression. PBR overexpression was also detected at the mRNA level as revealed by real-time PCR. The extent of PBR protein overexpression was equivalent in colorectal adenomas and carcinomas but slightly increased in metastases.

Conclusion: These data suggest a functional role of PBR during colorectal carcinogenesis and tumor spread. Thus, PBR qualifies as a target for innovative diagnostic and therapeutic approaches.

Literatur: Overexpression of the peripheral benzodiazepine receptor is a relevant prognostic factor in stage III colorectal cancer. Maaser K, Grabowski P, Sutter AP, Hopfner M, Foss HD, Stein H, Berger G, Gavish M, Zeitz M, Scherubl H. Clin Cancer Res. 2002;8:3205-9

Keywords: carcinogenesis and metastasis, colorectal cancer, peripheral benzodiazepine receptor (PBR), prognosis