Increased expression of matrix metalloproteinase 7 and 9 and membrane type 1-matrix metalloproteinase in esophageal squamous cell carcinomas.
BACKGROUND
The 5-year survival rate of patients with submucosal (sm) esophageal carcinoma continues to be much worse than that with intramucosal (m) lesions. The reasons are unclear, but matrix metalloproteinases (MMPs) and membrane type matrix metalloproteinases (MT-MMPs) are known to be involved in degradation of extracellular matrix macromolecules associated with tumor cell invasion. Expression of these enzymes may have some relation to the difference in survival between patients with sm and m esophageal carcinomas.


METHODS
Surgical specimens from 148 primary esophageal squamous cell carcinomas were examined for expression of MMP-1, 2, 3, 7, and 9; tissue inhibitor of MMP (TIMP)-1 and 2; MT1-MMP; and MT2-MMP by immunohistochemical staining. The results were compared with tumor progression and other clinicopathologic parameters. Localization of gelatinase activity was also confirmed in carcinoma cells by in situ zymography.


RESULTS
Expression of MMP-7 and 9, expression of MT1-MMP, and gelatinase activity were elevated in the carcinomas, correlating with depth of tumor invasion. Percentages of positive sm cases were 44.0%, 51.9%, and 52.0%, respectively, significantly higher than for the m cases. Percentages of venous invasion positive cases were 61.9%, 65.1%, and 65.1%, respectively.


CONCLUSIONS
Expression of MMP-7 and 9 and MT1-MMP is closely associated with invasion depth and venous invasion in esophageal squamous cell carcinomas.
Ohashi
K
K
Department of Pathology, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Nemoto
T
T
Nakamura
K
K
Nemori
R
R
D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053517:Matrix Metalloproteinase 15; D020783:Matrix Metalloproteinase 7 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000032:analysis*; D009361:Neoplasm Invasiveness; D015996:Survival Rate
C507098:MMP15 protein, human; D053517:Matrix Metalloproteinase 15; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9