OBJECTIVETo clarify the association of EGFR expression with angiogenesis and chemoresistance in ovarian cancer.

METHODSImmunohistochemical PV-6000 staining was used to detect the expression of EGFR, LRP protein and MVD in 102 ovarian tumor specimens.

RESULTSEGFR, LRP positive rates and MVD in borderline and malignant ovarian specimens were significantly higher than those in the normal and benign ones (P < 0.01). EGFR positive expression rate in stage III-IV carcinoma tissues, poor differentiation and with ascites was higher than that in stage I-II carcinomas of well differentiation and without ascites (P < 0.05). MVD was related to histological grade, residual tumor and ascites, LRP positive expression had no correlation with the clinicopathologic parameters (P > 0.05). The effective rate of chemotherapy in patients with EGFR and LRP-positive expression were 57.1% and 53.7%, respectively, significantly lower than that in cases with EGFR and LRP-negative expression (85.0% and 90.9%, P < 0.05). In the 64 cases with complete data, the three-year survival rate was 53.0%. The survival time was shorter in the cases with EGFR and LRP-positive expression, poor differentiation, ascites and chemoresistance (P < 0.01), and only LRP-positive expression and chemotherapeutic effect were independently related to survival time (P < 0.05). There was a correlation between EGFR and MVD (r = 0.548, P < 0.01), EGFR and LRP positive expression (P = 0.020).

CONCLUSIONThe expression of EGFR in ovarian cancer is related to angiogenesis and chemoresistance. EGFR and LRP-positive expression are related to chemoresistance, and detection of the two proteins may be helpful in guiding chemotherapy choice for ovarian cancer. LRP-positive expression and chemotherapeutic effect may be independent prognostic factors.

Antigens, CD34 ; metabolism ; Ascites ; pathology ; Cystadenocarcinoma, Mucinous ; blood supply ; drug therapy ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; blood supply ; drug therapy ; metabolism ; pathology ; Cystadenoma, Mucinous ; blood supply ; drug therapy ; metabolism ; pathology ; Cystadenoma, Serous ; blood supply ; drug therapy ; metabolism ; pathology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic ; pathology ; Ovarian Neoplasms ; blood supply ; drug therapy ; metabolism ; pathology ; Receptor, Epidermal Growth Factor ; metabolism ; Survival Rate ; Vault Ribonucleoprotein Particles ; metabolism

PURPOSE: Vascular endothelial growth factor (VEGF) levels in malignant ascites have high diagnostic value for their discrimination from asictes of non-malignant origin. However, there have been no reports on the comparison of VEGF levels between malignant ascites of chemonaive and chemotreated patients. MATERIALS AND METHODS: VEGF levels were measured in 44 ascites patients (cirrhosis ascites, 10; chemonaive patients, 21; chemotreated patients, 13) and compared to the level of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9). The diagnostic parameters of sensitivity, specificity, and correlation among 3 markers were evaluated. RESULTS: VEGF levels in malignant ascites of chemonaive and chemotreated patients were significantly higher than those in cirrhotic ascites (p<0.05). VEGF levels in ascites of chemonaive patients were significantly higher than those in chemotreated patients (p<0.05). A cutoff value of 10.4pg/mL was calculated using receiver operating characteristic curves (ROCs) for VEGF in chemotreated and chemonaive patients, which gave sensitivities of 75.0% and 53.8% and specificities of 69.6% and 47.1%, respectively. Positive correlations were observed between VEGF and CEA (r=0.353, p<0.05) as well as between VEGF and CA19-9 (r=0.367, p<0.05) in ascites. CONCLUSION: VEGF levels could be a useful tumor marker for malignant ascites, but its value should carefully be interpreted because of lesser reliability in chemotreated ones.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Ascites/*drug therapy/*metabolism/pathology ; CA-19-9 Antigen/metabolism ; Carcinoembryonic Antigen/metabolism ; Child ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Tumor Markers, Biological/metabolism ; Vascular Endothelial Growth Factor A/*metabolism