Ciappuccini Renaud, Saguet-Rysanek Virginie, Giffard Florence, Licaj Idlir, Dorbeau Marine, Clarisse Bénédicte, Poulain Laurent, Bardet Stéphane
Department of Nuclear Medicine and Thyroid Unit, Comprehensive Cancer Centre François Baclesse, 14000 Caen, France.
Normandie University, UNICAEN, INSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancers Prevention and Treatment), 14000 Caen, France.
J Clin Endocrinol Metab. 2021 Nov 19;106(12):3536-3545. doi: 10.1210/clinem/dgab563.
Little is known about prostate-specific membrane antigen (PSMA) expression in patients with cervical involvement of differentiated thyroid cancer (DTC).
We investigated PSMA expression in neck persistent/recurrent disease (PRD) using immunohistochemistry and the association with radioiodine (RAI) or 18-fluorodeoxyglucose (18FDG) uptake, and patient outcome.
DESIGN, SETTING, AND PATIENTS: Data from 44 consecutive DTC patients who underwent neck reoperation from 2006 to 2018 in a comprehensive cancer center.
MAIN OUTCOME MEASURE(S): Immunostaining was performed with vascular endothelial marker CD31 and PSMA. PSMA expression was quantified using the immunoreactive score (IRS). RAI and 18FDG uptake were assessed before surgery using posttherapeutic RAI scintigraphy and 18FDG positron emission tomography with computed tomography. Mean follow-up after reintervention was 6.5 ± 3.7 years.
Thirty patients (68%) showed at least 1 PSMA-positive lesion (IRS ≥ 2) with similar proportions in RAI-positive and RAI-negative patients (75% vs 66%). In RAI-negative patients, however, the proportion of PSMA-positive disease (79% vs 25%, P < 0.01) and the mean IRS (4.0 vs 1.0, P = 0.01) were higher in 18FDG-positive than in 18FDG-negative patients. Furthermore, mean IRS was higher in patients ≥ 55 years, large primary tumors (>40 mm) or aggressive subtypes, and was correlated with structural disease at last follow-up. Strong PSMA expression (IRS ≥ 9) was associated with shorter progression-free survival (PFS).
Our findings show that PSMA expression was present in two-thirds of patients with neck PRD, that it was related to poor prognostic factors and that very high expression was associated with poorer PFS. This preliminary study may offer new perspectives for the management of RAI-refractory DTC.
关于分化型甲状腺癌（DTC）伴宫颈受累患者中前列腺特异性膜抗原（PSMA）的表达情况，目前所知甚少。
我们采用免疫组织化学方法研究颈部持续性/复发性疾病（PRD）中PSMA的表达情况，以及其与放射性碘（RAI）或18-氟脱氧葡萄糖（18FDG）摄取及患者预后的关系。
设计、地点和患者：来自一家综合癌症中心2006年至2018年连续接受颈部再次手术的44例DTC患者的数据。
使用血管内皮标志物CD31和PSMA进行免疫染色。使用免疫反应评分（IRS）对PSMA表达进行定量。术前使用治疗后RAI闪烁显像和18FDG正电子发射断层扫描与计算机断层扫描评估RAI和18FDG摄取情况。再次干预后的平均随访时间为6.5±3.7年。
30例患者（68%）至少有1个PSMA阳性病变（IRS≥2），RAI阳性和RAI阴性患者中的比例相似（75%对66%）。然而，在RAI阴性患者中，18FDG阳性患者的PSMA阳性疾病比例（79%对25%，P<0.01）和平均IRS（4.0对1.0，P=0.01）高于18FDG阴性患者。此外，年龄≥55岁、原发肿瘤较大（>40mm）或侵袭性亚型的患者平均IRS更高，且与最后随访时的结构性疾病相关。PSMA强表达（IRS≥9）与无进展生存期（PFS）较短相关。
我们的研究结果表明，三分之二的颈部PRD患者存在PSMA表达，其与不良预后因素相关，且非常高的表达与较差的PFS相关。这项初步研究可能为难治性RAI的DTC治疗提供新的视角。
