Schulte K-M, Talat N, Galata G, Aylwin S, Izatt L, Eisenhofer G, Barthel A, Bornstein S R
Department of Endocrine Surgery, King's College Hospital, King's Health Partners, London, UK.
Department of Endocrinology, King's College Hospital, King's Health -Partners, London, UK.
Horm Metab Res. 2014 Dec;46(13):964-73. doi: 10.1055/s-0034-1383581. Epub 2014 Jul 11.
This study analyses new information on gene mutations in paragangliomas and puts them into a clinical context. A suspicion of malignancy is critical to determine the workup and surgical approach in adrenal (A-PGL) and extra-adrenal (E-PGL) paragangliomas (PGLs). Malignancy rates vary with location, family history, and gene tests results. Currently there is no algorithm incorporating the above information for clinical use. A sum of 1,821 articles were retrieved from PubMed using the search terms "paraganglioma genetics". Thirty-seven articles were selected of which 9 were analyzed. It was found that 599/2,487 (24%) patients affected with paragangliomas had a germline mutation. Of these 30.2% were mutations in SDHB, 25% VHL, 19.4% RET, 18.4% SDHD, 5.0% NF1, and 2.0% SDHC genes. A family history was positive in 18.1-64.3% of patients. Adrenal PGLs accounted for 55.1% in mutation (+) and 81.0% in mutation (-) patients (RR 1.2, p < 0.0001). Bilateral A-PGLs accounted for 56.4% in mutation (+) and 3.2% in mutation (-) patients (RR 8.7, p < 0.0001). E-PGL were found in 33.6% of mut+ and 17.3% of mut- (RR 1.7, p < 0.0001). In mutation (+) patients PGLs malignancy varied with location, adrenal (6.4%) thoraco-abdominal E-PGL (38%), H & N E-PGL (10%). Malignancy rates were 8.2% in mutation (-) and lower in mutation (+) PGLs except for SDHB 36.5% and SDHC 8.3%. Exclusion of a mutation lowered the probability of malignancy significantly in E-PGL (RR 0.03 (95% CI 0.1-0.6); p < 0.001). Mutation analysis provides valuable preoperative information to assess the risk of malignancy in A-PG and E-PGLs and should be considered in the work up of all E-PGL lesions.
本研究分析了副神经节瘤基因突变的新信息，并将其置于临床背景中。怀疑存在恶性肿瘤对于确定肾上腺（A-PGL）和肾上腺外（E-PGL）副神经节瘤（PGL）的检查方法和手术方式至关重要。恶性率因位置、家族史和基因检测结果而异。目前尚无将上述信息纳入临床应用的算法。使用搜索词“副神经节瘤遗传学”从PubMed检索到1821篇文章。筛选出37篇文章，其中9篇进行了分析。发现2487例副神经节瘤患者中有599例（24%）存在胚系突变。其中，30.2%为SDHB突变，25%为VHL突变，19.4%为RET突变，18.4%为SDHD突变，5.0%为NF1突变，2.0%为SDHC基因。18.1%-64.3%的患者有家族史。肾上腺PGL在突变（+）患者中占55.1%，在突变（-）患者中占81.0%（相对风险1.2，p<0.0001）。双侧A-PGL在突变（+）患者中占56.4%，在突变（-）患者中占3.2%（相对风险8.7，p<0.0001）。E-PGL在突变（+）患者中占33.6%，在突变（-）患者中占17.3%（相对风险1.7，p<0.0001）。在突变（+）患者中，PGL的恶性程度因位置而异，肾上腺为6.4%，胸腹E-PGL为38%，头颈部E-PGL为10%。突变（-）患者的恶性率为8.2%，除SDHB为36.5%和SDHC为8.3%外，突变（+）PGL的恶性率较低。排除突变可显著降低E-PGL的恶性概率（相对风险0.03（95%置信区间0.1-0.6）；p<0.001）。突变分析为评估A-PG和E-PGL的恶性风险提供了有价值的术前信息，应在所有E-PGL病变的检查中予以考虑。
