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The Loss of 5-Reductase Type I and Type II mRNA Expression in Metastatic Prostate Cancer to Bone and Lymph Node Metastasis

Prostate Research Group, University Departments of Oncology [F. K. H., M. R., C. W. B.], Medical Sciences [K. C.], Pathology [K. G.], and Urology [P. B.], Western General Hospital, Edinburgh, Scotland EH4 2XU, United Kingdom

Purpose: Considerable evidence has accumulated demonstrating that the 5-reduction of testosterone to dihydrotestosterone occurs more efficiently in the normal and benign hyperplastic prostate than in prostate cancer tissues. Efforts have also been channeled into investigating the distribution of 5-reductase isoenzymes in primary prostate tissues and in "in vitro" cell models of the human prostate. However, no one has, thus far, examined the expression of these isoenzymes in prostate cancer metastasis, although such studies might shed some light on the mechanism(s) responsible for the loss of hormone sensitivity in those tumors. The present report addresses this issue in the hope that this might help to identify the steps leading to the development of prostate cancer metastasis.

Experimental Design: In the present study we used in situ mRNA hybridization of sections from archival paraffin-embedded material to investigate the expression of 5-reductase type I (5R-I) and type II (5R-II) mRNAs in prostate cancer bony (n = 9) and lymph node (n = 13) metastasis, and compared the mRNA distributions with those observed in sections from primary prostate tumors (n = 12). In parallel, sections were investigated for androgen receptor (AR) mRNA expression, and immunostained for AR and prostate-specific antigen.

Results: Neither 5R-I nor 5R-II mRNA expression was detected in any of the prostate metastatic lesions, although the same metastatic sites expressed AR mRNA, and stained for cytoplasmic prostate-specific antigen and nuclear AR. In contrast, primary prostate tumors displayed intense staining for 5R-I and 5R-II.

Conclusion: These findings suggest that the loss of 5-reductase mRNA expression in bone and lymph node metastasis may be associated, in part, with the progression of these tumors to androgen insensitivity.

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