Alterd Expression Of PTEN And Tumor Related Genes In Normal Ovary, Benigh And Maligant Ovarian Lesions And Significance

ObjectiveTo observe the mutation or protein expression of PTEN or its related tumor suppressor genes during ovarian tumorigenesis, compare them with clinicopatho-logical feature of ovarian cancer and explore their roles in tumorigenesis and progression of ovarian cancer.Methods1. Mutated exon 5 of PTEN gene was examined in normal ovary (n = 10) , ovarian cyst (n = 10) , ovarian borderline tumor (n = 19) and ovarian cancer ( n = 95 ) by PCR - SSCP. Protein expression of PTEN gene was evaluated in corresponding tissues by using the immunohistochemistry. The mutation and protein expression of PTEN gene were compared with clinicopathological feature of ovarian cancer.2. We examined mRNA expression of PTEN and VEGF165 in normal ovary (n =5) , ovarian cyst (n =5) , ovarian borderline tumor (n =9) and epithelial ovarian cancer (n = 60 ) by RT - PCR. Their expressions were compared with clinicopathological feature of ovarian cancer. The relationship between their expressions was concerned in all ovarian samples as well.3. We observe the different expression profiles of PTEN, nm23Hj, VEGF165, Tiaml, MMP-2, TIMP-2, HE4, S100A4, 0 -actin and GAPDH genes in normal ovary and ovarian cancer tissue by cDNA microarray. Their expressions were compared with clinicopathological feature of ovarian cancer.Results1. Mutated exon 5 of PTEN gene was detected 5(6.6% ) cases in epitheli-umderived ovarian cancer and 1 (11.1%) case in metastastic ovarian cancer.2. Expression of PTEN protein was significantly lower in ovarian borderline tumor or ovarian cancer than that in normal ovary or ovarian cyst( P < 0. 05 ). PTEN expression was negatively correlated with clinicopathological staging of o-varian cancer( P <0. 01) , but positively with histological differentiation( P < 0. 01). Loss or reduced protein expression level of PTEN gene was related to lymph node metastasis of ovarian cancer (P <0. 01). Among ovarian epithelial cancer, endometrioid cancer expressed PTEN protein was the lowest level (P < 0.01).3. mRNA expression level of PTEN gene was significantly lower in ovarian borderline tumor or ovarian cancer than that in normal ovary or ovarian cyst( P < 0.05). mRNA expression level of PTEN gene was negatively correlated with clinicopathological staging(P <0.01) , whereas positively with histological differentiation ( P < 0. 01). mRNA expression level of PTEN gene was significantly lower in ovarian endometrioid cancer than ovarian serous or mucinous cancer( P< 0.01). mRNA expression level of VEGF165 gene was significantly higher in o-varian cancer than that in normal ovary or ovarian cyst( P < 0.01). mRNA expression level of VEGF165 gene was positively correlated with clinicopathological staging( P < 0. 01) , whereas negatively with histological differentiation ( P < 0. 05 ). mRNA expression level of VEGF165 gene was significantly higher in ovarian serous cancer than the other ovarian epithelial cancer ( P < 0.01). mRNA expression of VEGF165 gene was increased with mRNA expression level of PTEN gene reduced.4. In ovarian cancer, PTEN, TIMP -2 and nm23H, genes were downregu-lated, and which were negatively correlated with clinicopathological staging and lymph node metastasis of ovarian cancer( P <0.01) , while positively with histological differentiation ( P < 0. 01 ). Tiaml, VEGF165, MMP - 2, HE4 and S100A4 genes were up - regulated, and HE4 gene was up - regulated markedly,which were positively correlated with clinicopathological staging and lymph node metastasis of ovarian cancer(P <0. 01) , while negatively with histological differentiation ( P <0. 01). while there was no difference in expression of keep-house gene B - actin and GAPDH in normal ovary and ovarian cancer tissue.Conclusion1. Mutation of PTEN gene occurred in ovarian cancer. Down - regulated expression of PTEN was probably an important molecular event in tumorigenesis of ovarian cancer. Abnormal expression of PTEN gene was involved in progression of ovarian cancer probably by decreasing cell adhesion and...