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

Abstract

BackgroundTo 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.MethodsImmunohistochemistry 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.ResultsThe 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.ConclusionsPRL-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.

Expression of AGR2 in pituitary adenomas and its association with tumor aggressiveness

“…The tissues consisted �� 24 ���l�c���-��c�����g ��������, 24 Immunohistochemical staining. A streptavidin-peroxidase method was used for immunostaining, as previously described (12). Briefly, slides were deparaffinized with xylene ����� ����� (��� 5-10 ��� ��c�), ���������� ����� ����� �� � gradient series of ethanol (100, 95 and 75%), and rinsed with phosphate-buffered saline (PBS).…”

“…The slides were independently evaluated by two investigators under a light microscope (TE200; Nikon, Tokyo, Japan). As described previously (12), the staining intensity was scored as follows: 0, negative; 1, weak; 2, medium; and 3, strong. The extent of staining was scored as follows: 0, 0%; 1, 1-25%; 2, 26-50%; 3, 51-75%; and 4, 76-100%, according to the percentages of the positive staining area in relation to the whole carcinoma area.…”

Markery Proliferacji I Inwazyjności W Guzach Przysadki Wydzielających Hormon Wzrostu

“…On the other hand, in a RT-PCR study of different subtypes of pituitary adenomas, somatotropinomas showed lowest VEGF expression [29,30]. In IHC, expression of VEGF was decreased in somatotropinomas, against normal tissue [31].…”

Análise da expressão da filamina A nos tumores hipofisários e suas implicações clínicas e terapêuticas

“…Em nossa casuística, 63% das amostras de somatotropinomas expressaram DRD2 de forma moderada ou intensa (IRS ≥ 4), confirmando dados anteriormente publicados (176) . A eficácia da CAB no controle hormonal foi obtida em 30% dos somatotropinomas, compatível com os dados da literatura (72) .…”

“…A expressão frequente de DRD2 em ACNF também foi relatada anteriormente (155,159,176) , no entanto, sua correlação com resposta à CAB foi avaliada estatisticamente por apenas dois estudos (153,155) , sendo positiva em apenas um deles (153) .…”