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It is well documented that the binding of urokinase-type plasminogen activator(uPA) to its receptor (uPAR), which has been implicated in cancer invasion andmetastasis, is regulated by several inhibitors such as maspin. In this study,we investigated the interrelationship between clinicopathologic findings and expressionof uPA, uPAR and maspin in oral squamous cell carcinoma (OSCC) to elucidate theparticipation of maspin in the uPA/uPAR system in the malignant behavior of OSCC.Using immunohistochemical techniques to examine the expression levels of uPA,uPAR and maspin in 54 cases of OSCC, we also compared the clinicopathologic featuresof OSCC with the expression levels of each. Moreover, we examined the expressionof uPA, uPAR and maspin in six cell lines derived from OSCC using reverse transcriptase-polymerasechain reaction (RT-PCR) and Western blotting. uPA and uPAR showed a positive correlationwith the mode of cancer invasion; conversely maspin showed a negative correlationwith the mode of invasion. Multivariate analysis revealed that only two factors(N-category and uPA+/uPAR+/maspin- expression pattern) were significant and independentvariables with relative risks of 3.84 and 2.52, respectively. In particular, tumorsexhibiting an expression pattern of uPA+/uPAR+/maspin- were highly malignant andwere associated with the worst survival rate (5-year overall survival rate, 29.4%),while tumors with an expression pattern, uPA-/uPAR-/Μaspin+, showed the most favorablesurvival rate (5-year overall survival rate, 77.8%). In vitro, lower expressionof maspin was also noted in the cell lines derived from grade 4D OSCC, which exhibiteda stronger invasive potential than the cells lines derived from the other gradesof OSCC, while uPA and uPAR demonstrated an expression trend opposite to maspin.These results indicate that uPA, uPAR and maspin expression patterns may be usefulmarkers for evaluating the clinical course or prognosis of OSCC patients.

oncology reports

Expression of urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor and maspin in oral squamous cell carcinoma: Association with mode of invasion and clinicopathological factors