Expression And Significance Of VEGF And Its Receptors In Epithelial Ovarian Carcinoma

Objectives:(1) To study the expression of VEGF and its soluble receptor sFlt1 in serum, ascitic fluids and tumor cysts of patients with ovarian neoplasms, and evaluate the value of serum VEGF in the diagnosis and prognosis of ovarian cancer patients.(2) To assess the expression of VEGF and its receptor KDR in ovarian epithelial cancer cell lines(3A0, ES2). And to elucidate whether or not anti-angiogenesis peptides influence directly the growth of ovarian cancer cell lines(3A0, ES2) in vitro. Methods:(1) To measure VEGF, sFlt1(cancer group n=20) in the preoperative serum of patients with ovarian cancer (n=34), benign cysts(n=20), control cases(n=20). and also to investigate the serum VEGF levels at the first month, the third month , the sixth month after operation by ELISA. Furthermore, to assess the VEGF, sFlt1 levels in ascitic fluids and tumor cysts of patients with ovarian cancer and compare serum VEGF with the serum CA125 in cancer patients .(2) To measure the expression of VEGF and its receptor KDR in ovarian cancer cell lines (3A0, ES2) by ELISA, Immunocytochemistry, RT-PCR and the effect of anti-angiogenesis peptide in vitro by MTT.Results:(1) VEGF levels was significantly elevated in the serum of cancer patients compared with patients who had benign neoplasms or control cases(P<0. 001), while there was no difference between benign neoplasms and control cases. The difference of serum VEGF levels between FIGOI and IK HI* IV showed no significant (P>0.05) . The differences between VEGF levels in serum in relation to age% histological subtypes> FIGO stages .. grade> ascitic fluids volumes of ovarian cancer were statistically insignificant ( P>0. 05 ) .In cancer patients , significantly higher VEGF levels were detected in ascitic fluids and/or tumor cysts than that in corresponding serum (K0. 001) . After operation, the VEGF levels decreased gradually . At the third month, serum VEGF was almost as much as that in non-cancer patients (P>0. 05). One patient with high persistent serum VEGF levels relapsed.(2) The ability of VEGF to differentiate malignancy from benign masses at a cut-off VEGF levels of 492 pg/ml gave a sensitivity of 76. 5%, a specificity of 75% , a positive predictive value of 75. 4%, a negative predictive value of 76.1% with the analysis of ROC curve . There were 70% (7/10) cases with serum VEGF beyond 492 pg/ml in FIGO I cancer group.(3) Preoperative serum sFltl levels decreased significantly compared with benign neoplasms and control cases (FKO. 001) ,but showed no statistically difference between benign neoplasms and control cases. The VEGF/sFltl increased by 10 times in epithelial cancer group compared with control cases. The differences between sFltl levels in serum in relation to age> histological subtypes^ grade^ FIGO stages of ovarian cancer were statistically insignificant (P>0. 05). The sFltl levels in ascitic fluids and/or tumor cysts was significantly higher than that in corresponding serum CFKO. 05) . The postoperative sFltl levels increased gradually and it was up to control cases levels after one month .(4)After operation, both serum VEGF and CA125 decreased down to levels of control cases at the third month. The preoperative serum VEGF levelswas not associated with the serum sFltl levels (r=0. 306 P>0. 05) or with the serum CA125 levels (r=0.023 P>0.05) in ovarian cancer patients.(5) Preoperative serum VEGF appeared not to be associated significantly with progress-free survival (Log-rank test 0. 67 P>0. 05) and overall survival(Log-rank test 0.60 P>0. 05).(6) VEGF was detected in culture medium of ovarian cancer cell lines (3A0, ES2) by ELISA.(7) VEGF mRNA was detected in ovarian cancer cell lines (3ACK ES2) by RT-PCR and VEGF was found in cytoplasms of ovarian cell lines by immunocheraistry. KDR was positive stained in ES2, while negative in 3A0.(8) Anti-angiogenesis peptide was not observed to inhibit the growth of ovarian cancer cells obviously by MTT in vitro.Conclusions:(l)VEGF was an important factor during the development of ovarian cancer. The serum preoperative VEGF was an promising marker in differentiating malignancy from benign tumor with ovarian neoplasms; The serum VEGF increased significantly at early stage with a positive rate of 70%, so it maybe useful in early diagnosis of ovarian cancer; The changes of postoperative serum VEGF levels were helpful to supervise the development of ovarian cancer. In cancer group, statistically higher VEGF levels were detected in ascitic fluids and/or tumor cysts than that in corresponding serum. (2)sFltl,as a soluble VEGF receptor and also an intrinsic ^ negative regulator of angiogenesis , decreased in the serum of cancer group. The dramatic elevation of VEGF/sFltl in cancer group indicated the body...