HIF-1α And Its Relationship To Proliferation And Apoptosis And Angiogenesis In Epithelial Ovarian Tumor

Objective: To investigate the expression of hypoxia inducible factor-1α(HIF-1α) mRNA and protein in epithelial ovarian tumors, and explore its relationship to proliferation, apoptosis and angiogenesis, and know better its function in the occurrence and development of epithelial ovarian carcinoma, which is useful to clinical diagnosis and therapy. Methods: 77 cases of diagnosed primary epithelial ovarian tumors and metastases and normal ovarian tissues were obtained in our hospital from 2002.3 to 2004.7, including (1) 27 cases of primary epithelial ovarian cancer tissue. The mean age of patients was 50 years, including 14 cases <50 years and 13 cases≥50years. There were 14 cases of serous adenocarcinoma, 7 cases of mucinous adenocarcinoma and 6 cases of other adenocarcinoma. Stage of disease was determined according to FIGO criteria in 1986: 9 cases were in Ⅰ～Ⅱstage, and 18 cases were in Ⅲ～Ⅳstage. Grading: 15 cases were G1, and 12 cases were G2～G3. As well as we had the CA125 results of 15 cases. (2) 11 cases of retrieved metastases, the mean age of patients was 49 years. (3) 9 cases of ovarian borderline tumor, including 5cases of boderline serous cystadenoma and 4cases of boderline mucinous cystadenoma. The mean age of patients was 46 years. (4) 18 cases of ovarian cystadenomas, including 5 cases of serous cystadenoma and 13 cases of mucinous cystadenoma. The mean age of patients was 49 years. (5) 12 cases of normal ovarian tissues. The mean age of patients was 52 years. There was no difference of the patients'age in every group. All patients hadn't chemotherapy, immune therapy and radical therapy. All tissue samples were fixed in 10% buffered formalin, and embedded in paraffin in 48 hours after the operation. Serial sections (5μm) from each specimen were cut, transferred to slides, and then analyzed. Expression of HIF-1αmRNA and protein were determined in situ hybridization techniques and S-P immunohistochemistry. Expression of Ki67-LI, VEGF and CD105-MVD were determined by S-P immunohistochemistry. The apoptotic rate (AI) of tumor cells was determined in terminal deoxynucl neotidy transferase mediated UTP nick end labeling (TUNEL). Results: (1) HIF-1αprotein expression was localized in the plasma or nucleus of tumor cells, especially in the plasma. In cancer primary tissues and metastases, HIF-1αprotein expressed mainly in randomly scattered fashion, and also in some endothelial cells of vessels. HIF-1αprotein expression was not observed in the epithelial cells of normal ovarian tissues. From cystadenomas to borderline tumors to primary cancer tissues to metastases, the positive ratio of HIF-1αprotein was 16.67%, 77.78%, 74.07% and 81.82%. There was no difference of HIF-1αprotein expression in borderline tumors and cancers andmetastases (P>0.05), but HIF-1αprotein expression was higher than in cystadenomas and normal ovarian tissues (P<0.05). (2) HIF-1αmRNA expression was also primarily localized in the plasma or nucleus of tumor cells. In 74.07% primary cancer tissues, 90.91% metastases, and 66.67% borderline tumors, overexpression of HIF-1αmRNA was observed, which was higher than in cystadenomas (P<0.05). There was no expression of HIF-1αmRNA in normal ovarian tissues. (3) In the primary cancer tissues, expression of HIF-1αmRNA and protein didn't correlate with the patients'age, the level of CA125, histological types and FIGO stages (P>0.05), but correlated with histological grade (P<0.05), and increased as histological grade increased. (4) With the development of tumors from benign to malignant, expression of LI, AI, VEGF and CD105-MVD increased (p<0.05). LI and CD105-MVD were higher in epithelial ovarian cancers than in borderline tumors and than in cystadenomas (P<0.05), but weren't different between primary cancer tissues and metastases, as well as cystadenomas and normal ovarian tissues (P>0.05). AI was in primary tissues of epithelial ovarian cancer> borderline tumors> cystadenomas (P<0.05). VEGF expression was higher in primary tissues of epithelial ovarian cancers than in bor...