| Objective:To investigate the expression of HIF-1αand VEGF proteins in epithelial ovarian neoplasms and their clinical significance;using MTT chemosensitivity assay To detect the sensitivity of specimens of primary epithelial ovarian carcinoma to four chemotherapeutic drugs used alone as well as combination in vitro; To analyse the relationship between the expression of HIF-1αprotein and chemosensitivity of epithelial ovarian carcinomas in vitro.Methods:1 Expressions of HIF-1αand VEGF proteins in 42 epithelial ovarian carcinomas, 12 borderline tumors , 18 benign cystadenomas and 7 normal ovarian tissues was detected by immunohistochemistry method. 2 The expression of HIF-1αproteins in 18 cases of fresh primary epithelial ovarian cancer tissues was determined by western-blot method. 3 MTT assay was used to detect the chemosensitivity of 18 cases of ovarian carcinoma fresh specimens to Anticancer drugs as follows:paclitaxel (TAX), doxorubion(ADM), topotecan (TPT) , cisplatin(DDP),used alone as well as combination in vitro.Results:1 Immunohistochemistry staining: (1)HIF-1αprotein was staining in the nuclear or plasma , there is no expressing of HIF-1αin normal ovarian tissues ,the expressing rate in benign cystadenomas,borderline tumors and ovarian carcinomas was 16.67%,50.00%,64.29%, respectively.The expression rate of HIF-1αprotein in PEOC and ovarian borderline tumors was significantly higher than that in ovarian benign adenomas.(P<0.05); In epithelial ovarian carcinomas, the expression of HIF-1αprotein was correlated with pathologic grade and lymphatic or greater omentum metastasis (P<0.05),but not with histological type,clinical stage or age(P>0.05).With the pathologic grade gets lower, the expression of HIF-1αgoes up. (2) VEGF protein was staining only in the plasma,VEGF protein was expressed both in normal ovarian tissues and ovarian tumors .the expressing rate of VEGF protein in normal ovarian tissues was 14.29%, in benign cystadenomas, borderline tumors and ovarian carcinomas the expressing rate was 44.44%,75.00%,88.10%, respectively.VEGF protein level in ovarian carcinomas were much higher than that in other ovarian tissues(P<0.05), the expression of VEGF protein was correlated with clinical stage, pathologic grade and lymphatic or greater omentum metastasis(P<0.05),its the expression elevated as the clinical stage increased and the pathologic grade decreased, but not with histological type or age(P>0.05). (3) The co-expression rate of HIF-1αand VEGF proteins was 71.43%(30/42),there was a significantly inverted relationship between the expression of HIF-1 and VEGF protein.2 Western-blot:the protein band of HIF-1αis at 120KD,In 18 cases of PEOC specimens , the expression rate of HIF-1αprotein was 61.11%(11/18), close to the result of the immunohistochemistry staining.3 MTT chemosensitivity assay : Evaluable test results were achieved in 17 of 18 specimens, the evaluability rate of MTT was 94.44%. The ex vivo sensitive rate of TAX was 82.35%(14/17), of DDP was 58.82%(10/17), of ADM was 47.06%(8/17),of TPT was 23.53%(4/17) ; the combination sensitive rate of TAX+DDP, ADM+DDP, TPT+DDP was 88.24%, 58.82%, 70.59% respectively; the expression of HIF-1αprotein was associated with resistance to DDP and ADM in vitro (P<0.05), in the case of PEOC with resistance to TAX,TPT, the expression of HIF-1αprotein were higher than those with sensitive to TAX,TPT samples, but there was no obvious difference (P>0.05).Conclusion:1 HIF-1αprotein was overexpression in epithelial ovarian carcinomas, and its overexpression was correlated with pathologic grade and lymphatic or greater omentum metastasis; There was overexpression of VEGF protein in epithelial ovarian carcinoma, and its overexpression was correlated with clinical stage, pathologic grade and lymphatic or greater omentum metastasis. Overexpression of HIF-1αand VEGF proteins might play synergetic roles in carcinogenesis and evolution of epithelial ovarian carcinoma.2 Overexpression of HIF-1αprotein was positively associated with VEGF protein expression. HIF-1αmay induces the tumor angiogenesis by elevated the expression of VEGF protein and play an important role in oncogenesis and metastasis of tumor.3 The positive expression of HIF-1αprotein was correlated with the resistance to DDP and ADM in PEOC. Further clinical studies in a large group of patients were needed for confirmation whether expression of HIF-1αprotein could become a useful marker to predict the resistance in epithelial ovarian cancer patients.
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