Expression Of E-cadherin And Urokinase-type Plasminogen Activator In Meningiomas Associated With Invasiveness

Meningiomas present twenty percents in intracalvarium primar tumor, it is generally considered to be benign, and can be surgically resected with great success in most cases, but in some circumstances these tumors can pose some of the most difficult questions. Malignant meningiomas are highly invasive, which can invade menings, skull and extracranial tissues, some of them even metastasize extracranialy. Some meningiomas are benign in histology but have the invasive behavior biologically. This can make it difficult to resect them completely and become the reason for recurring after operation. At present, studies on the invasive behavior of meningiomas are still less and the exact mechanisms of which are not understood completely. Studies show that meningiomas have the same mechanisms of invasiveness as other tumors, which include three steps. (1)Tumor cells cling to extracellular matrix(ECM).(2) The local ECM is degraded enzymes which are secreted from tumorcells. (3) Tumor cells migrate to the regions where the matrix has been degraded by enzymes of tumor cells. E-cadherin is a calcium-dependented transmembrane protein, its low-expresses will damp the sticking between tumor cell, and tumor cell is easy to fall off and to migrate, which lead to tumor invasiveness and metastasize. uPA is a serine proteinase ,it can change plasminogen into fibrinolysin, the latter can degrade brinolase and fiber adherence protein of ECM and basal membrane, which lead to tumor invasive and metastasize. The roles of E-cadherin and uPA in invasiveness meningiomas, and the relationships between E-cadherin and uPA in meningiomas, have received little attention in domestic and foreign literature. In the current study, we investigated the expression of E-cadherin and uPA protein in meningiomas, and analyzed how their expression relates to histological grade, and invasiveness of meningiomas. Further more, this investigation was also to devise a new strategy for understanding the biological behavior, predicting theprognosis, and remedy of meningiomas.Materials and methods1. A total of 60 meningioma patients, who have integrity data of pathology and clinic,underwent neurosurgical procedures at the Department of Neurosurgery, the First Affiliated Hospital, Zhengzhou University, from Jan 2002 to June 2006. The histological distribution in the group studied was40 benign (WHO Grade I , ncluding 8 mixed pattern 7 meningothelial, 10 fibrous, 8 fibrous-endepidermis, 4 angiomatous 5 psammomatous), 10 atypical (WHO Grade II),and 10 anaplastic/ malignant (WHO Grade III)meningiomas.2. In 60 cases of patients, tumor histopathology and aggressive behavior were evaluated.3. Streptavidin-Peroxidase(S-P) immunohistochemistry technique was used to detectthe expression of E-cadherin and uPA protein in 60 meningiomas4. Statistical analysis was performed by the SPSS 13.0 software package. Differences among groups were analyzed by using the Chi-squared test. Associations between two variables were assessed by the Spearman correlation test. All of the P values resulted from two-sided statistical test. Statistical significant level was consideredas "alpha equals 0.05"Results 1. The expression of E-cadherin in meningiomas present in cell membrane and incell-substance, which present cell-substance mostly. The positive rate of E-cadherin in 10 specimens of normal brain tissue was 100% and was 69.2% in 60 specimens of meningiomas. The difference between those was significant (P<0.05).The expression of E-cadherin in grade II and grade IIImeningiomas were not different from those in grade I meningiomas (P>0.05).The expression of E-cadherin in invasive meningiomas were lower than those in noninvasive meningiomas. The difference between those was significant (P<0.05).2. The expression of uPA in meningiomas present in cell-substance. The expression ofuPA in 10 specimens of normal brain tissue were all negative. The positive rate of uPA was 82.7% in 60 specimens of meningiomas. The difference between those was significant (P<0.05).The expressions of uPA were significant higher in grade II and gradeIII meningiomas than those in grade I meningiomas, in which the expression of uPA was significant higher than those in the normal human brain tissues (P<0.05). The expression of uPA in invasive meningiomas were higher than those in noninvasive meningiomas. The difference between those was significant (P<0.05).3. There is a significant negative correlation between the expression of E-cadherinand uPA protein(r=-0.329 P<0.05). However, detect of E-cadherin and uPA protein weren't clearly correlated with the patients' age, gender, and tumor location (P>0.05)Conclusions1. The expression of E-cadherin protein in meningiomas was lower than those innormal human brain tissue. E-cadherin protein play a important role in the development and invasion of meningiomas.2. Meningiomas mostly express uPA. uPA protein accumulation correlated withthe development, the degree of maligance, and the invasiveness of meningiomas.3. There is a significant negative correlation between the expression of E-cadherinand uPA. Significant correlation was observed between low-expression of E-cadherin and high-expression of uPA with the invasion of the meningiomas. 4. Meningiomas cells cling to extracellular matrix(ECM) and The local ECM is degraded enzymes which are secreted from meningiomas cells, which play a important role in the invasiveness of meningiomas.5. The expression of E-cadherin and uPA are important biological markers reflectingthe malignance and the invasiveness of meningiomas.