Platelet-derived growth factor receptor expression and amplification in choroid plexus carcinomas
Platelet-derived growth factor receptor expression and amplification in choroid plexus carcinomas
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DOI：
10.1038/modpathol.3800989
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发表时间：
2008-03-01
期刊：
影响因子：
7.5
通讯作者：
Hasselblatt, Martin
中科院分区：
文献类型：
--
作者：
Nupponen, Nina N.;Paulsson, Janna;Hasselblatt, Martin
血小板源性生长因子（PDGF）受体信号转导与神经胶质瘤的发展有关，但尚未在脉络丛癌中进行研究，脉络丛癌是一种预后不良的儿科肿瘤，需要新的治疗方案。因此，PDGF受体α和β的蛋白表达，以及各自的基因，PDGFRA和PDGFRB的扩增状态，在一系列的22例患有脉络丛癌，使用免疫组化和显色原位杂交（CISH）进行了检查。大多数脉络丛癌表达PDGF受体，其中6例（27%）显示PDGF受体α的高染色评分，13例（59%）显示PDGF受体β的高染色评分。相应地，在12例CISH病例中的8例中观察到PDGFRA拷贝数增加，1例显示扩增（每个核6个或更多信号）。PDGFRB扩增的脉络丛癌比例更高（5/12例）。PDGFRB扩增状态与PDGF受体β蛋白表达评分显著相关（P = 0.01，斯皮尔曼）。PDGF受体α或PDGF受体β的表达状态与无进展生存期无显著相关。总之，PDGF受体，特别是PDGF受体β的表达和扩增在脉络丛癌中很常见，这为开发针对这些罕见恶性儿科肿瘤的PDGF受体信号传导的治疗提供了第一个基本原理。
Platelet-derived growth factor (PDGF) receptor signaling has been implicated in the development of glial tumors, but not yet been examined in choroid plexus carcinomas, pediatric tumors with dismal prognosis for which novel treatment options would be desirable. Therefore, protein expression of PDGF receptors alpha and beta as well as amplification status of the respective genes, PDGFRA and PDGFRB, were examined in a series of 22 patients harboring choroid plexus carcinoma using immunohistochemistry and chromogenic in situ hybridization (CISH). The majority of choroid plexus carcinomas expressed PDGF receptors with 6 cases (27%) displaying high staining scores for PDGF receptor alpha and 13 cases (59%) showing high staining scores for PDGF receptor beta. Correspondingly, copy-number gains of PDGFRA were observed in 8 cases out of 12 cases available for CISH and 1 case displayed amplification (six or more signals per nucleus). The proportion of choroid plexus carcinomas with amplification of PDGFRB was even higher (5/12 cases). PDGFRB amplification status and PDGF receptor beta protein expression scores were significantly correlated (P = 0.01, Spearman). Expression status of PDGF receptor alpha or PDGF receptor beta was not significantly associated with progression-free survival. To conclude, expression and amplification of PDGF receptors, particularly PDGF receptor beta, are frequent in choroid plexus carcinomas, providing a first rationale for the development of treatments targeting PDGF receptor signaling in these rare malignant pediatric tumors.