Relationship between expression of vascular endothelial growth factor and the proliferation of prolactinomas.

OBJECTIVE: Prolactinomas are the most common functional hormone-producing pituitary lesions, accounting for 30-40% of all pituitary tumors, while in autopsy series their incidence reaches 50%. However, patients with prolactinoma had a higher recurrence percentage and rate than patients with acromegaly or Cushing's disease. Furthermore, prolactinomas have the highest rate of recurrence post-surgery as compared with other pituitary adenomas. At present, this behavior of prolactinoma is largely unexplained, but may be related to definition of cure, or to more frequent microscopic tumor infiltration into normal pituitary tissue, which is not removed at surgery. Many factors may influence the proliferation of pituitary adenomas, such as angiogenesis, apoptosis, growth factors, oncogenes, tumor suppressor genes, and hormone receptors. Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and vascular permeability of various brain tumors. But, little is known about the role of VEGF expression in the process of the growth of prolactinomas. The purpose of this study is to investigate the relationship between VEGF expression and the growing of prolactinomas.

METHODS: VEGF expression was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) in 18 prolactinomas. Clinical factors to investigate were age, gender, hormonal functioning, and radiological findings of pituitary adenomas. Radiological findings which were investigated by magnetic resonance (MR) images were tumor size. The relationship between these factors and VEGF expression was statistically analyzed.

RESULTS: VEGF was expressed in all cases (100%). VEGFA mRNA and VEGFB mRNA were expressed in all examined pituitary adenomas; the mean expression level of VEGFA mRNA was 8.67±1.59; and the mean expression level of VEGFB mRNA was 10.01±2.67. There was no significant difference in the VEGFA mRNA and VEGFB mRNA expression level among the adenomas we examined(P=0.24). There was no significant correlation between VEGFA and VEGFB mRNA expression and patient age, gender, and tumor size. However, The expression of VEGFA mRNA significantly (P<0.001)decreased in tumor groups compared to the control groups. And the expression of VEGFB mRNA significantly (P<0.05) decreased in tumor groups compared to the control groups as well.

CONCLUSIONS: This study suggests that angiogenesis in prolactinomas may not be primarily mediated by VEGF pathway, and low level of VEGF expression may not always have significant influence in prolactinomas with a higher recurrence percentage and rate.