Expression of vascular endothelial growth factor in growth hormone-secreting pituitary adenomas: special reference to the octreotide treatment

Objective: The present study was designed to investigate the localization of VEGF in GH-secreting pituitary adenomas and to evaluate the characteristic differences of VEGF expression in relation to the clinical effect of preoperative treatment with octreotide. Methods: Fifty-six cases of GH-secreting adenomas, which were divided into three groups and three normal pituitary glands, were studied using immunohistochemistry for expression of VEGF. The octreotide group consisted of 33 patients who received the octreotide before the surgery. The bromocriptine group consisted of 11 patients who received bromocriptine orally. The control groups consisted of 12 patients who were not treated with octreotide or bromocriptine pre-operatively. VEGF staining patterns for each specimen were examined under light microscopy and graded in a scale. These findings were correlated with clinical characteristics. Results: VEGF was displayed in a diffuse cytoplasmic pattern in all cases. VEGF staining was strongly seen in the cytoplasm in normal pituitary glands. Moderately positive staining with VEGF appeared in six of 33 (18%) cases of the octreotide group, and in eight of 12 (67%) cases of the control group. In contrast, weakly positive staining was observed in 25 of 33 (76%) cases of the octreotide group, and in three of 12 (25%) cases of the control group. The staining pattern differs statistically between the octreotide and control group, typically in densely granulated GH cell adenomas. Weak staining with VEGF appeared in all ten cases in which the tumor had shrunk. Age, gender, tumor size, tumor invasiveness and adenoma type did not influence VEGF expression. Conclusion: We conclude that octreotide may inhibit the angiogenesis through down-regulation of VEGF.