VEGF, flt-1, and KDR/flk-1 as prognostic indicators in endometrial carcinoma.
OBJECTIVE
Tumor angiogenesis is a highly regulated process under the influence of the host microenvironment and mediators. Studies of breast cancer and, more recently, ovarian and cervical cancer, demonstrate that neovascularization correlates with the likelihood of metastasis and recurrence. Vascular endothelial growth factor (VEGF), an important regulator of tumor angiogenesis in the endometrium, flt-1, and KDR/flk-1 are good markers of vascular proliferation. Being that angiogenesis is a precursor to the development of progressive disease, we hypothesize that quantifying VEGF, flt-1, and KDR/flk-1 expression in uterine malignancies is a superior predictor of metastatic potential and survival than is FIGO grade of tumor, depth of invasion, and histology.


METHODS
The histologic slides of 47 patients with uterine malignancies (35 adenocarcinomas, 6 papillary serous, and 6 carcinosarcomas) were reviewed. The paraffin blocks from the primary tumor were obtained. Immunohistochemistry staining was performed for VEGF, flt-1, and KDR/flk-1. Microvessel density, used to analyze VEGF and receptor concentrations, was determined by two independent investigators, who were blinded to the patients clinical status. The impact of VEGF, flt-1, and KDR/flk-1 as well as stage, grade, depth of invasion, and nodal status on the incidence of metastases, recurrence, and survival was determined using logistic regression analysis and product limit life system survival analysis, respectively.


RESULTS
Results indicated that when evaluating all three histologic types, only stage and grade of tumor were found to impact upon the incidence of recurrence and survival. When patients with carcinosarcoma and papillary serous adenocarcinoma were excluded from the analysis, once again only stage and grade of tumor were significant prognostic indicators of recurrence and survival. Only grade of tumor and depth of uterine invasion were significant predictors of a tumor's metastatic potential. VEGF, flt-1, and KDR/flk-1 proved to be of little significance in predicting metastases, recurrence, and survival. Patients with advanced disease in all three histologic subtypes often had low VEGF and receptor positivity.


CONCLUSIONS
In this study, VEGF, flt-1, and KDR/flk-1 receptor concentrations did not correlate with the incidence of metastases, recurrence, and survival.
Fine
B A
BA
Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78284, USA.
Valente
P T
PT
Feinstein
G I
GI
Dey
T
T
D000230:Adenocarcinoma / Q000098:blood supply / Q000473:pathology* / Q000556:secondary; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D018450:Disease Progression; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000098:blood supply / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000032:analysis*; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000032:analysis*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging / Q000379:methods; D009389:Neovascularization, Pathologic; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D017978:Receptors, Growth Factor / Q000032:analysis*; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1