MMP-3 mRNA and MMP-3 and MMP-1 proteins in bladder cancer: a comparison with clinicopathologic features and survival.
Matrix metalloproteinases (MMPs) are proteolytic enzymes important at several points during multistep neoplastic progression. Although MMP-1 and MMP-3 have been implicated in the progression of various human cancers, their expression in bladder cancer has not been addressed. Immunohistochemistry (Strept-ABC-HRP method) and in situ hybridization were performed to detect MMP-1 protein, MMP-3 protein, and MMP-3 mRNA, respectively, in 59 transitional cell bladder carcinomas. To assess the role of these MMPs in bladder cancer, their expression was evaluated in relation to known clinicopathologic parameters and patients' disease-free and overall survival. Immunoreactivity for MMP-1 and MMP-3 proteins was observed in the cytoplasm of cancer cells in 30.5% and 24% of samples, respectively. Transcripts for MMP-3 mRNA were localized in stromal cells in 71.2% of cases and in cancer cells in 49% of cases. MMP-1 immunoreactivity demonstrated a statistically significant association with deeply invasive and grade III tumors versus superficial and lower grade tumors. MMP-3 protein immunoreactivity and MMP-3 mRNA immunolocalization did not associate with the parameters studied. However, MMP-3 mRNA localization in stromal cells demonstrated a borderline association with poor patients' disease-free and overall survival. In conclusion, the authors' results demonstrate a differential expression between MMP-1 and MMP-3 in bladder cancer; MMP-1 appears to participate in invasiveness and possibly in loss of differentiation in urothelial carcinomas in contrast to MMP-3.
Nakopoulou
L
L
Department of Pathology, Medical School, The National and Kapodistrian University of Athens, Greece. lnakopou@cc.uoa.gr
Gakiopoulou
H
H
Zervas
A
A
Giannopoulou
I
I
Constantinides
C
C
Lazaris
A C
AC
Liapis
H
H
Kyriakou
G
G
Dimopoulos
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000201:enzymology* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016016:Proportional Hazards Models; D017154:Stromal Cells / Q000201:enzymology / Q000378:metabolism; D015996:Survival Rate; D001743:Urinary Bladder / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000401:mortality / Q000473:pathology
D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1