Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Front Endocrinol (Lausanne). 2023 Mar 16;14:1121397. doi: 10.3389/fendo.2023.1121397. eCollection 2023.
Pheochromocytomas and paragangliomas (PCC/PGL) are rare neuroendocrine tumors and can secrete catecholamine. Previous studies have found that SDHB immunohistochemistry (IHC) can predict SDHB germline gene mutation, and SDHB mutation is closely associated with tumor progression and metastasis. This study aimed to clarify the potential effect of SDHB IHC as a predictive marker for tumor progression in PCC/PGL patients.
We included PCC/PGL patients diagnosed in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from 2002 to 2014 for retrospective analysis and discovered that SDHB (-) staining patients had poorer prognoses. Then we examined SDHB protein expression by IHC on all tumors in the prospective series, which was composed of patients from 2015 to 2020 in our center.
In the retrospective series, the median follow-up was 167 months, and during follow-up, 14.4% (38/264) patients developed metastasis or recurrence, and 8.0% (22/274) patients died. Retrospective analysis revealed that 66.7% (6/9) of participants in the SDHB (-) group and 15.7% (40/255) of those in the SDHB (+) group developed progressive tumors (OR: 10.75, 95% CI: 2.72-52.60, P=0.001), and SDHB (-) was independently associated with poor outcomes after adjusting by other clinicopathological parameters (OR: 11.68, 95% CI: 2.58-64.45, P=0.002). SDHB (-) patients had shorter disease-free survival (DFS) and overall survival (OS) (P<0.001) and SDHB (-) was significantly associated with shorter median DFS (HR: 6.89, 95% CI: 2.41-19.70, P<0.001) in multivariate cox proportional hazard analysis. In the prospective series, the median follow-up was 28 months, 4.7% (10/213) patients developed metastasis or recurrence, and 0.5% (1/217) patient died. For the prospective analysis, 18.8% (3/16) of participants in the SDHB (-) group had progressive tumors compared with 3.6% (7/197) in the SDHB (+) group (RR: 5.28, 95% CI: 1.51-18.47, P=0.009), statistical significance remained (RR: 3.35, 95% CI: 1.20-9.38, P=0.021) after adjusting for other clinicopathological factors.
Our findings demonstrated patients with SDHB (-) tumors had a higher possibility of poor outcomes, and SDHB IHC can be regarded as an independent biomarker of prognosis in PCC/PGL.
嗜铬细胞瘤和副神经节瘤（PCC/PGL）是罕见的神经内分泌肿瘤，可分泌儿茶酚胺。先前的研究发现，SDHB 免疫组化（IHC）可预测 SDHB 种系基因突变，SDHB 突变与肿瘤进展和转移密切相关。本研究旨在阐明 SDHB IHC 作为 PCC/PGL 患者肿瘤进展预测标志物的潜在作用。
我们纳入了 2002 年至 2014 年在上海交通大学医学院瑞金医院诊断的 PCC/PGL 患者进行回顾性分析，发现 SDHB（-）染色患者的预后较差。然后，我们在中心前瞻性系列中对所有肿瘤进行了 SDHB 蛋白表达的 IHC 检测，该系列包括 2015 年至 2020 年的患者。
在回顾性系列中，中位随访时间为 167 个月，随访期间 14.4%（38/264）的患者发生转移或复发，8.0%（22/274）的患者死亡。回顾性分析显示，SDHB（-）组的 66.7%（6/9）和 SDHB（+）组的 15.7%（40/255）的患者发生进展性肿瘤（OR：10.75，95%CI：2.72-52.60，P=0.001），并且 SDHB（-）在调整其他临床病理参数后与不良预后独立相关（OR：11.68，95%CI：2.58-64.45，P=0.002）。SDHB（-）患者的无病生存率（DFS）和总生存率（OS）更差（P<0.001），并且在多变量 Cox 比例风险分析中，SDHB（-）与中位 DFS 显著相关（HR：6.89，95%CI：2.41-19.70，P<0.001）。在前瞻性系列中，中位随访时间为 28 个月，4.7%（10/213）的患者发生转移或复发，0.5%（1/217）的患者死亡。对于前瞻性分析，SDHB（-）组的 18.8%（3/16）的患者发生进展性肿瘤，而 SDHB（+）组的 3.6%（7/197）（RR：5.28，95%CI：1.51-18.47，P=0.009），在调整其他临床病理因素后，统计学意义仍然存在（RR：3.35，95%CI：1.20-9.38，P=0.021）。
我们的研究结果表明，SDHB（-）肿瘤患者发生不良预后的可能性更高，SDHB IHC 可作为 PCC/PGL 的独立预后标志物。
