IN-SITU HYBRIDIZATION STUDIES OF METALLOPROTEINASE-2 AND METALLOPROTEINASE-9 AND TIMP-1 AND TIMP-2 EXPRESSION IN HUMAN PROSTATE-CANCER

The expression of MMP-2, MMP-9, TIMP-1, TIMP-2, and the urokinase rece ptor were examined in fetal and normal prostate tissues, benign prosta tic hyperplasia and prostate cancer (n = 117), In situ hybridization w ith digoxigenin-labeled oligonucleotide probes demonstrated that TIMP- 1 and TIMP-2 were expressed at elevated levels in the stroma of Gleaso n sum 5 tissues, whereas MMP-2 and MMP-9 tr ere expressed at relativel y 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 expresse d. Furthermore, TIMP-1 and TIMP-2 expression was high in organ-confine d specimens (OC, n = 43), somewhat lon er in specimens with capsular p enetration (CP, n = 29), and low or negative in samples with surgical margin/seminal vesicle (M/SV, n = 17) and IS mph node (LN, n = 13) inv olvement, In contrast, MMP-2 and MMP-9 expression was low in the OC ti ssues; and noticeably higher in CP, M/SV, and LN specimens. Finally, c orrelation of TIMP and MMP expression with GS and pathological stage v ersus cure rate further revealed that a high percentage of organ-confi ned, GS 5 specimens expressing TIMP and little MMP were cured. In comp arison, few of the GS 7-10 patients with capsular penetration and expr essing MMP and little TIMP were cured, The data suggest that TIMP-1 (a nd TIMP-2) and MMP-2 (and MMP-9) are independent predictors of outcome .