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

Clin Exp Metastasis. 1997 May;15(3):246-58. doi: 10.1023/a:1018421431388.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Collagenases / analysis
  • Collagenases / genetics*
  • Follow-Up Studies
  • Gelatinases / analysis
  • Gelatinases / genetics*
  • Glycoproteins / analysis
  • Glycoproteins / genetics*
  • Humans
  • In Situ Hybridization*
  • Male
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Metalloendopeptidases / analysis
  • Metalloendopeptidases / genetics*
  • Neoplasm Staging
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Proteins / analysis
  • Proteins / genetics*
  • RNA, Messenger / analysis
  • Tissue Inhibitor of Metalloproteinase-2
  • Tissue Inhibitor of Metalloproteinases


  • Glycoproteins
  • Proteins
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinases
  • Tissue Inhibitor of Metalloproteinase-2
  • Collagenases
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9