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Overexpression of the Peripheral Benzodiazepine Receptor Is a Relevant Prognostic Factor in Stage III Colorectal Cancer¹

Medical Clinic I [K. M., P. G., A. P. S., M. H., M. Z., H. S.], Institute of Pathology [H-D. F., H. S.], and Department of Surgery [G. B.], University Hospital Benjamin Franklin, Free University of Berlin, 12200 Berlin, Germany, and Department of Pharmacology, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 31096 Haifa, Israel [M. G.]

Purpose: The peripheral benzodiazepine receptor (PBR) has been implicated in the growth control of colorectal cancer, where PBR-specific ligand-binding is increased 3–4-fold. However, the prognostic relevance of PBR (over) expression has not yet been evaluated in colorectal cancer.

Experimental Design: A 5-year follow-up was performed in 116 consecutive patients undergoing surgery for colorectal cancer with regional or distant metastases [Union International Contre le Cancer (UICC) stage III, 59 patients; UICC stage IV, 57 patients]. The monoclonal anti-PBR antibody 8D7 was used for immunohistochemical examination of paraffin-embedded sections. PBR-specific staining was compared in cancer tissues and normal mucosa. Kaplan-Meier survival curves were calculated.

Results: Twenty-eight % of the colorectal cancers strongly overexpressed PBR. The mean survival of patients with stage III cancer was 56.2 ± 9.2 months with and 86.8 ± 6.6 months without high overexpression of PBR (P = 0.006). Univariate and multivariate analyses revealed that high PBR overexpression is an independent unfavorable prognostic factor in stage III colorectal cancer. In stage IV, however, the PBR status did not correlate with different survival times.

Conclusions: Strong PBR overexpression is a new independent prognostic marker in stage III colorectal cancer. Evaluating PBR overexpression may be useful for stratifying risk and developing risk-adapted strategies of adjuvant therapy.

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