Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors.
Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors.
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DOI：
10.1007/s12020-013-0093-x
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发表时间：
2014-06
期刊：
影响因子：
3.7
通讯作者：
Ben-Shlomo, Anat
中科院分区：
文献类型：
--
作者：
Cooper, Odelia;Mamelak, Adam;Bannykh, Serguei;Carmichael, John;Bonert, Vivien;Lim, Stephen;Cook-Wiens, Galen;Ben-Shlomo, Anat
由于ErbB信号传导是催乳素合成的决定因素，因此检测了ErbB受体在催乳素瘤结局和治疗中的作用。本研究的目的是描述催乳素瘤中ErbB受体表达的特征，然后进行一项用靶向酪氨酸激酶抑制剂（TKI）治疗耐药催乳素瘤的初步研究。三级转诊中心催乳素瘤回顾性分析和多巴胺受体激动剂耐药催乳素瘤的初步研究。我们对29例切除的催乳素瘤组织进行了EGFR、ErbB2、ErbB3和ErbB4的免疫荧光染色，并与临床特征相关。2例侵袭性耐药泌乳素瘤患者入组并完成试验。他们每天接受拉帕替尼1250 mg，持续6个月，并进行肿瘤和激素评估。主要结果指标为各自ErbB受体的阳性肿瘤染色、催乳素水平的治疗性降低和肿瘤缩小。在接受TKI治疗的2例受试者中，治疗的PRL水平和肿瘤体积均受到抑制。EGFR在腺瘤中的阳性表达率为82%，ErbB2为92%，ErbB3为25%，ErbB4为71%，ErbB2评分> EGFR>ErbB4>ErbB3。ErbB3的高表达与视交叉受压（p = 0.03）、鞍上扩张（p = 0.04）和颈动脉包绕（p= 0.01）相关。在ErbB3表达较高的肿瘤中观察到较高的DA反应率。催乳素瘤特异性ErbB受体的表达与肿瘤侵袭、症状和对多巴胺激动剂的反应相关靶向ErbB受体可能是耐药泌乳素瘤患者的有效治疗方法。
As ErbB signaling is a determinant of prolactin synthesis, role of ErbB receptors was tested for prolactinoma outcomes and therapy. The objective of this study was to characterize ErbB receptor expression in prolactinomas and then perform a pilot study treating resistant prolactinomas with a targeted tyrosine kinase inhibitor (TKI). Retrospective analysis of prolactinomas and pilot study for dopamine agonist resistant prolactinomas in tertiary referral center. We performed immunofluorescent staining of a tissue array of 29 resected prolactinoma tissues for EGFR, ErbB2, ErbB3, and ErbB4 correlated with clinical features. Two patients with aggressive resistant prolactinomas enrolled and completed trial. They received lapatinib 1250 mg daily for 6 months with tumor and hormone assessments. Main outcome measures were positive tumor staining of respective ErbB receptors, therapeutic reduction of prolactin levels and tumor shrinkage. Treated PRL levels and tumor volumes were suppressed in both subjects treated with TKI. EGFR expression was positive in 82% of adenomas, ErbB2 in 92%, ErbB3 in 25%, and ErbB4 in 71%, with ErbB2 score > EGFR>ErbB4>ErbB3. Higher ErbB3 expression was associated with optic chiasm compression (p = 0.03), suprasellar extension (p = 0.04), and carotid artery encasement (p= 0.01). Higher DA response rates were observed in tumors with higher ErbB3 expression. Prolactinoma expression of specific ErbB receptors is associated with tumor invasion, symptoms, and response to dopamine agonists. Targeting ErbB receptors may be effective therapy in patients with resistant prolactinomas.
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影响因子：
3.8
作者：
Kim J;Jeong H;Lee Y;Kim C;Kim H;Kim A
通讯作者：
Kim A
影响因子：
4
作者：
Jaffrain-Rea, ML;Petrangeli, E;Gulino, A
通讯作者：
Gulino, A
影响因子：
--
作者：
Fukuoka, Hidenori;Cooper, Odelia;Melmed, Shlomo
通讯作者：
Melmed, Shlomo
影响因子：
3.4
作者：
Leake, R;Barnes, D;Walker, R
通讯作者：
Walker, R
影响因子：
15.9
作者：
Fukuoka, Hidenori;Cooper, Odelia;Melmed, Shlomo
通讯作者：
Melmed, Shlomo