Prognostic significance of matrix metalloproteinases-2 activation ratio in renal cell carcinoma.
BACKGROUND
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. MMP-2 and MMP-9 have been reported to be closely associated with tumor invasion and metastasis in various human carcinomas.


METHODS
Tissue samples were obtained from 57 patients with renal cell carcinoma (RCC) who underwent radical nephrectomy in our hospital. We examined the expression of MMPs by gelatin zymography and assessed correlations with clinico-pathological parameters and clinical outcomes.


RESULTS
We detected bands corresponding to MMP-9, proMMP-2 and active MMP-2. The expression of active MMP-2 and MMP-2 activation ratio (active MMP-2/[proMMP-2 and active MMP-2]) were higher in T3 tumors than in T1 and T2 tumors. There were no significant differences in the expression of proMMP-2, active MMP-2 or MMP-9 for any of the clinico-pathological parameters. Patients with high MMP-2 activation ratio or high MMP-9 had significantly worse cause-specific survival. Interestingly, among patients with stage III RCC, those with high MMP-2 activation ratio or high active MMP-2 had significantly worse cause-specific survival. Univariate analysis showed that histological grade (P = 0.0001), histologic type (P = 0.0005), MMP-2 activation ratio (P = 0.0159), stage (P = 0.0001), MMP-9 (P = 0.0316), and T (primary tumor) category of TNM (primary tumor, lymph node, metastasis) classification (P = 0.0021) were significant predictors of clinical outcome. Multivariate analysis showed that only histological grade (P = 0.002) and stage (P = 0.0099) were independently significant predictors of clinical outcome.


CONCLUSIONS
Activation of MMP-2 appears to play important roles in initiating metastasis, as shown by results obtained with stage III RCC patients. However, further study is needed to confirm this.
Takahashi
Masayuki
M
Department of Urology, School of Medicine, University of Tokushima, Tokushima, Japan.
Oka
Natuo
N
Naroda
Takushi
T
Nishitani
Masa-Aki
MA
Kanda
Kazuya
K
Kanayama
Hiro-Omi
HO
Kagawa
Susumu
S
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020782:Matrix Metalloproteinases / Q000032:analysis*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009392:Nephrectomy; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2