Relationship between metalloprotease expression in tumour and stromal cells and aggressive behaviour in prostate carcinoma: Simultaneous high-throughput study of multiple metalloproteases and their inhibitors using tissue array analysis of radical prostatectomy samples.
OBJECTIVE
The aim of this study was to detect a potential association between clinicopathological factors of prostate cancer aggressiveness and the expression of matrix metalloproteases and their inhibitors in tumour and stromal cells.


METHODS
A tissue array technique and immunochemistry with specific antibodies against matrix metalloproteinases (MMPs)-1, 2, 7, 9, 11, 13, 14, and their tissue inhibitors (TIMPs)-1, 2 and 3 were used to analyse the surgical specimens of 133 patients treated by radical prostatectomy. For each antibody preparation, the cellular location of immunoreactivity was determined.


RESULTS
The expression of MMP-2 was negatively associated with high tumour grade. With regard to stromal fibroblasts, TIMP-3 expression was positively associated with histological grade. MMP-7 expression was negatively associated with pretreatment serum levels of PSA, whereas MMP-13 was positively associated with higher levels of the antigen. TIMP-2 expression by mononuclear inflammatory cells correlated significantly and negatively with tumour grade.


CONCLUSIONS
The expression of TIMP-3 by fibroblasts was associated with a higher Gleason score. An increased expression of MMP-13 by fibroblasts was associated with a greater preoperative level of PSA. In contrast, MMP-2 expression by tumour as well as TIMP-2 expression by peritumoral inflammatory cells was associated with less aggressive prostate carcinoma characteristics.
Department of Urology, Hospital Central de Asturias, Oviedo, Spain.
Jesus
J
Fernandez-Gomez
Safwan
S
Escaf
Luis-Ovidio
LO
Gonzalez
Aurelio
A
Suarez
Salome
S
Gonzalez-Reyes
Jose
J
González
Oscar
O
Miranda
Francisco
F
Vizoso
D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D057166:High-Throughput Screening Assays; D006801:Humans; D008297:Male; D045726:Metalloproteases / Q000378:metabolism*; D008875:Middle Aged; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism; D046888:Tissue Array Analysis; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D019714:Tissue Inhibitor of Metalloproteinases; D045726:Metalloproteases