Matrix metalloproteinase-9 expression in bladder washes from bladder cancer patients predicts pathological stage and grade

• Published in: Clinical cancer research Vol. 4; no. 12; pp. 3011 - 3016
• Main Authors: F J Bianco, Jr, D C Gervasi, R Tiguert, D J Grignon, J E Pontes, J D Crissman, R Fridman, D P Wood, Jr
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-12-1998
• Subjects: Adult; Aged; Biological and medical sciences; Biomarkers, Tumor - biosynthesis; Collagenases - biosynthesis; Female; Humans; Male; Matrix Metalloproteinase 9; Medical sciences; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Nephrology. Urinary tract diseases; Tumors of the urinary system; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Urinary tract. Prostate gland; Human; Biological fluid; Urinary system disease; Enzyme; Gene product; Metalloendopeptidases; Urinary tract disease; Malignant tumor; Gene expression; Gelatinase B; Gelatinase A; Peptidases; Urinary bladder; Hydrolases; Advanced stage; Bladder disease; Diagnosis
• ISSN: 1078-0432; 1557-3265

The matrix metalloproteinases (MMPs), in particular the gelatinases (MMP-2 and MMP-9) have been associated with tumor cell
invasion and metastasis in many human cancers. Here we examined the expression of proMMP-2 (gelatinase A) and proMMP-9 (gelatinase
B) proteins in the cellular component of bladder washes obtained from 65 patients. Twenty-six patients had active bladder
cancer, 24 had a history of bladder cancer but no evidence of active disease at the time of cystoscopy (recurrence-free),
and 15 patients had lesions other than bladder cancer (controls). The results were correlated with the cytological findings
of the bladder wash and the histopathological results of the tumor resection when performed. In patients with active transitional
cell carcinoma of the bladder, 71 and 38% had expression and overexpression of the latent form of MMP-9 (proMMP-9), respectively.
In contrast, neither latent nor active MMP-2 could be detected in any of the samples examined, regardless of tumor status.
Overexpression of proMMP-9 correlated with higher grade (P = 0.003) and pathological stage (P = 0.04) of disease in the active
bladder cancer group. No significant gelatinase expression was detected in the recurrence-free and control cases. Compared
with urine cytology, proMMP-9 expression had an overall higher sensitivity for bladder cancer identification (71 versus 54%,
P = 0.11). Detection of proMMP-9 in bladder washes may be a novel approach for the identification of patients with more aggressive
forms of bladder cancer.