Lussey-Lepoutre Charlotte, Bellucci Alexandre, Burnichon Nelly, Amar Laurence, Buffet Alexandre, Drossart Tom, Fontaine Sébastien, Clement Olivier, Benit Paule, Rustin Pierre, Groussin Lionel, Meatchi Tchao, Gimenez-Roqueplo Anne-Paule, Tavitian Bertrand, Favier Judith
Department of Nuclear Medicine, Sorbonne Université, AP-HP, Pitie-Salpêtrière Hospital, F-75013, Paris, France.
PARCC, INSERM, Equipe Labellisée par la Ligue contre le Cancer, F-75015, Paris, France.
Eur J Nucl Med Mol Imaging. 2020 Jun;47(6):1510-1517. doi: 10.1007/s00259-019-04633-9. Epub 2019 Dec 13.
Germline mutations in genes encoding succinate dehydrogenase (SDH) are frequent in patients with pheochromocytoma and paraganglioma (PPGL). They lead to SDH inactivation, mediating a massive accumulation of succinate, which constitutes a highly specific biomarker of SDHx-mutated tumors when measured in vitro. In a recent pilot study, we showed that magnetic resonance spectroscopy (H-MRS) optimized for succinate detection (SUCCES) could detect succinate in vivo in both allografted mouse models and PPGL patients. The objective of this study was to prospectively assess the diagnostic performances of H-MRS SUCCES sequence for the identification of SDH deficiency in PPGL patients.
Forty-nine patients presenting with 50 PPGLs were prospectively enrolled in our referral center for H-MRS SUCCES. Two observers blinded to the clinical characteristics and genetic status analyzed the presence of a succinate peak and confronted the results to a composite gold standard combining PPGL genetic testing and/or in vitro protein analyses in the tumor.
A succinate peak was observed in 20 tumors, all of which had proven SDH deficiency using the gold standard (17 patients with germline SDHx mutations, 2 with a somatic SDHD mutation, and 1 with negative SDHB IHC and SDH loss of function). A false negative result was observed in 3 tumors. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of H-MRS SUCCES were respectively 87%, 100%, 100%, 90%, and 94%.
Detection of succinate using H-MRS is a highly specific and sensitive hallmark of SDH-deficiency in PPGLs.
编码琥珀酸脱氢酶（SDH）的基因种系突变在嗜铬细胞瘤和副神经节瘤（PPGL）患者中很常见。这些突变导致SDH失活，介导琥珀酸大量积累，在体外测量时，琥珀酸是SDHx突变肿瘤的高度特异性生物标志物。在最近的一项初步研究中，我们表明针对琥珀酸检测优化的磁共振波谱（H-MRS）（SUCCES）能够在同种异体移植小鼠模型和PPGL患者体内检测到琥珀酸。本研究的目的是前瞻性评估H-MRS SUCCES序列对PPGL患者中SDH缺陷的诊断性能。
49例患有50个PPGL的患者被前瞻性纳入我们的转诊中心进行H-MRS SUCCES检查。两名对临床特征和基因状态不知情的观察者分析了琥珀酸峰的存在情况，并将结果与结合PPGL基因检测和/或肿瘤体外蛋白质分析的综合金标准进行对照。
在20个肿瘤中观察到琥珀酸峰，使用金标准证实所有这些肿瘤均存在SDH缺陷（17例种系SDHx突变患者，2例体细胞SDHD突变患者，1例SDHB免疫组化阴性且SDH功能丧失患者）。在3个肿瘤中观察到假阴性结果。H-MRS SUCCES的敏感性、特异性、阳性预测值、阴性预测值和准确性分别为87%、100%、100%、90%和94%。
使用H-MRS检测琥珀酸是PPGL中SDH缺陷的高度特异性和敏感标志。
