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In situ hybridization studies of metalloproteinases 2 and 9 and TIMP-1 and TIMP-2 expression in human prostate cancer

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Abstract

The expression of MMP-2, MMP-9, TIMP-1, TIMP-2, and the urokinase receptor were examined in fetal and normal prostate tissues, benign prostatic hyperplasia and prostate cancer (n=117). In situ hybridization with digoxigenin-labeled oligonucleotide probes demonstrated that TIMP-1 and TIMP-2 were expressed at elevated levels in the stroma of Gleason sum 5 tissues, whereas MMP-2 and MMP-9 were expressed at relatively low levels. In higher Gleason sum tissues (GS 8-10), TIMP-1 and TIMP-2 were not expressed, whereas MMP-2 and MMP-9 were intensely expressed. Furthermore, TIMP-1 and TIMP-2 expression was high in organ-confined specimens (OC, n=43), somewhat lower in specimens with capsular penetration (CP, n=29), and low or negative in samples with surgical margin/seminal vesicle (M/SV, n=17) and lymph node (LN, n=13) involvement. In contrast, MMP-2 and MMP-9 expression was low in the OC tissues; and noticeably higher in CP, M/SV, and LN specimens. Finally, correlation of TIMP and MMP expression with GS and pathological stage versus cure rate further revealed that a high percentage of organ-confined, GS 5 specimens expressing TIMP and little MMP were cured. In comparison, few of the GS 7-10 patients with capsular penetration and expressing MMP and little TIMP were cured. The data suggest that TIMP-1 (and TIMP-2) and MMP-2 (and MMP-9) are independent predictors of outcome.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Allegheny University of Health Sciences, Broad and Vine St, Philadelphia, PA, USA

    M. Wood , K. Fudge , F. Garcia , Min Wang  & M. E. Stearns

  2. Departments of Surgery/Division of Urology and Pathology and the UNC-Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    J. L. Mohler

  3. Department of Pathology, The George Washington University Medical Center, Washington, DC, USA

    A. R. Frost

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  1. M. Wood
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  2. K. Fudge
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  6. Min Wang
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Wood , M., Fudge , K., Mohler , J.L. et al. In situ hybridization studies of metalloproteinases 2 and 9 and TIMP-1 and TIMP-2 expression in human prostate cancer. Clin Exp Metastasis 15, 246–258 (1997). https://doi.org/10.1023/A:1018421431388

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