Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Endocr Relat Cancer. 2019 May;26(5):539-550. doi: 10.1530/ERC-19-0024.
Pheochromocytoma and paraganglioma (PPGL) can be divided into at least four molecular subgroups. Whether such categorizations are independent factors for prognosis or metastatic disease is unknown. We performed a systematic review and individual patient meta-analysis aiming to estimate if driver mutation status can predict metastatic disease and survival. Driver mutations were used to categorize patients according to three different molecular systems: two subgroups (SDHB mutated or wild type), three subgroups (pseudohypoxia, kinase signaling or Wnt/unknown) and four subgroups (tricarboxylic acid cycle, VHL/EPAS1, kinase signaling or Wnt/unknown). Twenty-one studies and 703 patients were analyzed. Multivariate models for association with metastasis showed correlation with SDHB mutation (OR 5.68 (95% CI 1.79-18.06)) as well as norepinephrine (OR 3.01 (95% CI 1.02-8.79)) and dopamine (OR 6.39 (95% CI 1.62-25.24)) but not to PPGL location. Other molecular systems were not associated with metastasis. In multivariate models for association with survival, age (HR 1.04 (95% CI 1.02-1.06)) and metastases (HR 6.13 (95% CI 2.86-13.13)) but neither paraganglioma nor SDHB mutation remained significant. Other molecular subgroups did not correlate with survival. We conclude that molecular categorization accordingly to SDHB provided independent information on the risk of metastasis. Driver mutations status did not correlate independently with survival. These data may ultimately be used to guide current and future risk stratification of PPGL.
嗜铬细胞瘤和副神经节瘤(PPGL)可至少分为四个分子亚组。这些分类是否为独立的预后或转移疾病因素尚不清楚。我们进行了系统回顾和个体患者荟萃分析,旨在评估驱动突变状态是否可以预测转移疾病和生存。根据三种不同的分子系统,使用驱动突变对患者进行分类:两个亚组(SDHB 突变或野生型)、三个亚组(假缺氧、激酶信号或 Wnt/未知)和四个亚组(三羧酸循环、VHL/EPAS1、激酶信号或 Wnt/未知)。分析了 21 项研究和 703 名患者。多变量模型显示,与转移相关的因素与 SDHB 突变(OR 5.68(95%CI 1.79-18.06))以及去甲肾上腺素(OR 3.01(95%CI 1.02-8.79))和多巴胺(OR 6.39(95%CI 1.62-25.24))相关,但与 PPGL 位置无关。其他分子系统与转移无关。在与生存相关的多变量模型中,年龄(HR 1.04(95%CI 1.02-1.06))和转移(HR 6.13(95%CI 2.86-13.13)),但无论是副神经节瘤还是 SDHB 突变都不再具有显著意义。其他分子亚组与生存无关。我们得出的结论是,根据 SDHB 的分子分类为转移风险提供了独立的信息。驱动突变状态与生存无独立相关性。这些数据最终可能被用于指导当前和未来的 PPGL 风险分层。
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