Plasma methoxytyramine: a novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and SDHB mutation status.
Plasma methoxytyramine: a novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and SDHB mutation status.
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DOI：
10.1016/j.ejca.2011.07.016
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发表时间：
2012-07
影响因子：
8.4
通讯作者：
Pacak, Karel
中科院分区：
文献类型：
--
作者：
Eisenhofer, Graeme;Lenders, Jacques W. M.;Siegert, Gabriele;Bornstein, Stefan R.;Friberg, Peter;Milosevic, Dragana;Mannelli, Massimo;Linehan, W. Marston;Adams, Karen;Timmers, Henri J.;Pacak, Karel
关键词：
目前尚无可靠的生物标志物用于恶性嗜铬细胞瘤和paragangliomas（PPGLS）。这项研究检查了儿茶酚胺及其代谢物的测量是否可能为此目的提供效用。
受试者包括365例PPGL患者，包括105例转移酶，参考人群为846例，没有肿瘤。研究了十八个与儿茶酚胺相关的分析物，该分析物与琥珀酸脱氢酶亚基B（SDHB）的肿瘤位置，大小和突变有关。
接收器操作的特征曲线表明，血浆甲氧基抑制胺（O-甲基化的多巴胺代谢产物）提供了最准确的生物标志物，用于区分有或没有转移的患者。与没有转移的患者相比，血浆甲氧基因胺高4.7倍，与肿瘤负担无关的差异以及相关的1.6至1.8倍的去甲肾上腺素和诺甲肾上腺素。血浆甲氧基因胺增加与SDHB突变和肾上腺外疾病有关，但在没有SDHB突变和转移的患者中也存在于肾上腺肿瘤继发的转移的患者中。与SDHB突变相关的恶性肿瘤的高风险反映了肿瘤的大尺寸和肾外部位，这都是转移性疾病的独立预测因子。高于0.2 nmol/l或高于5 cm的肿瘤直径高于0.2 nmol/l的血浆甲氧基胺素表明转移性扩散的可能性增加，尤其是与肾上腺外部位置相关时。
血浆甲氧基因胺是转移性PPGL的一种新型生物标志物，与SDHB突变状态，肿瘤大小和位置一起提供了有用的信息，以评估恶性肿瘤的可能性并管理受影响的患者。
There are currently no reliable biomarkers for malignant pheochromocytomas and paragangliomas (PPGLs). This study examined whether measurements of catecholamines and their metabolites might offer utility for this purpose. Subjects included 365 patients with PPGLs, including 105 with metastases, and a reference population of 846 without the tumor. Eighteen catecholamine-related analytes were examined in relation to tumor location, size and mutations of succinate dehydrogenase subunit B (SDHB). Receiver-operating characteristic curves indicated that plasma methoxytyramine, the O-methylated metabolite of dopamine, provided the most accurate biomarker for discriminating patients with and without metastases. Plasma methoxytyramine was 4.7-fold higher in patients with than without metastases, a difference independent of tumor burden and the associated 1.6- to 1.8-fold higher concentrations of norepinephrine and normetanephrine. Increased plasma methoxytyramine was associated with SDHB mutations and extra-adrenal disease, but was also present in patients without SDHB mutations and metastases or those with metastases secondary to adrenal tumors. High risk of malignancy associated with SDHB mutations reflected large size and extra-adrenal locations of tumors, both independent predictors of metastatic disease. A plasma methoxytyramine above 0.2 nmol/L or a tumor diameter above 5 cm indicated increased likelihood of metastatic spread, particularly when associated with an extra-adrenal location. Plasma methoxytyramine is a novel biomarker for metastatic PPGLs that together with SDHB mutation status, tumor size and location provide useful information to assess the likelihood of malignancy and manage affected patients.
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影响因子：
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作者：
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