The expression profile of Dopamine D2 receptor, MGMT and VEGF in different histological subtypes of pituitary adenomas: a study of 197 cases and indications for the medical therapy

Zhengfeng Lu ,Youwei Wang,Wanchun Li,Chiyuan Ma,Mamatemin Tohti,Sheng Wang,Yuebing Hu,Junyang Li

doi:10.1186/preaccept-1232491055121159

Abstract

To study the expression of D2R, MGMT and VEGF for clinical significance in pituitary adenomas, and to predict the potential curative medical therapy of dopamine agonists, temozolomide and bevacizumab on pituitary adenomas. Immunohistochemistry and western blot were performed to detect the expression of expression of D2R, MGMT and VEGF in pituitary adenoma tissue samples. The ratio of high expression of D2R, MGMT or VEGF in different subtypes of PA was compared by the use of chi-squared tests. The relationships between D2R, MGMT and VEGF expression were assessed by the Spearman rank correlation test. The association between their expression and clinical parameters was analyzed using a chi-squared test, or Fisher's exact probability test when appropriate. The data showed that in 197 different histological subtypes of pituitary adenomas (PAs), 64.9% of them were D2R high expression, 86.3% were MGMT low expression and 58.9% were VEGF high expression. D2R high expression existed more frequently in PRL- and GH- secreting PAs. MGMT low expression existed in all PA subtypes. VEGF high expression existed more frequently in PRL, ACTH, FSH secreting and non-functioning PAs. The data of western blot also support the results. Spearman's rank correlation analysis showed that expression of MGMT was positively associated with D2R (r = 0.154, P = 0.031) and VEGF (r = 0.161, P = 0.024) in PAs, but no correlation was showed between D2R and VEGF expression (r = −0.025, P = 0.725 > 0.05). The association between their expression and clinical parameters was analyzed using a chi-squared test, or Fisher's exact probability test when appropriate, but the result showed no significant association. PRL-and GH-secreting PAs exist high expression of D2R, responding to dopamine agonists; Most PAs exist low expression of MGMT and high expression of VEGF, TMZ or bevacizumab treatment could be applied under the premise of indications.

Highlights

To study the expression of D2 receptors (D2R), methylguanine DNA methyltransferase (MGMT) and vascular endothelial growth factor (VEGF) for clinical significance in pituitary adenomas, and to predict the potential curative medical therapy of dopamine agonists, temozolomide and bevacizumab on pituitary adenomas
The positive expression of D2R was detected in 194 tissues, of MGMT was in all tissues and of VEGF was in 190 tissues
The proportions of cases showing low or high expression levels for D2R, MGMT and VEGF in different subtypes of Pituitary adenoma (PA) were shown in Table 1. 64.9% of 197 PAs were D2R high expression, 86.3% of them were MGMT low expression and 58.9% of them were VEGF high expression

Summary

Introduction

To study the expression of D2R, MGMT and VEGF for clinical significance in pituitary adenomas, and to predict the potential curative medical therapy of dopamine agonists, temozolomide and bevacizumab on pituitary adenomas. More and more studies demonstrated the inspiring therapeutic effect of TMZ on pituitary carcinomas and aggressive PAs. As a DNA repairase, O6-methylguanine DNA methyltransferase (MGMT) confers chemoresistance to TMZ [9]. Bevacizumab is a monoclonal antibody which has been approved by USA FDA to treat colorectal cancer, non-small-cell lung carcinoma, breast cancer, renal carcinoma and recurrent glioma [10]. It blocks vascular endothelial growth factor (VEGF) binding to its receptor [11].

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