Circulating Myeloid-Derived Suppressor Cells Predict Differentiated Thyroid Cancer Diagnosis and Extent
Circulating Myeloid-Derived Suppressor Cells Predict Differentiated Thyroid Cancer Diagnosis and Extent
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DOI：
10.1089/thy.2015.0289
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发表时间：
2016-03-01
期刊：
影响因子：
6.6
通讯作者：
Epstein, Alan L.
中科院分区：
文献类型：
--
作者：
Angell, Trevor E.;Lechner, Melissa G.;Epstein, Alan L.
背景：对于一些患者来说，建立分化型甲状腺癌（DTC）的术前诊断和长期预后仍然具有挑战性。骨髓源性抑制细胞（MDSC）是介导免疫耐受的肿瘤诱导细胞，可在癌症患者的外周血中检测到。作者之前开发了一种新的临床测定法来检测外周血中两种人类 MDSC 亚群的表型，并假设通过该测定法测得的较高 MDSC 水平与恶性肿瘤和较差的患者预后呈正相关。方法：对因孤立性甲状腺结节而接受甲状腺切除术的患者进行了一项前瞻性观察性试点研究。通过超声检查证实存在>1cm的甲状腺结节，并且所有病例在手术前均进行了细针抽吸活检。使用基于流式细胞术的新型免疫测定法对术前收集的外周血进行分析，以检测和量化人类 MDSC 的两个子集。通过组织病理学诊断、分期和治疗后是否存在持续性疾病来比较循环 MDSC 水平。结果：本研究纳入的 50 名患者中，47 名 (94%) 的 MDSC 测量成功。一名患者被发现患有并发癌症，留下 46 名患者进行初步分析。 46 个结节中，5 个（10.8%）细胞学诊断为良性，5 个（10.8%）为异型性或意义不明的滤泡性病变，5 个（10.8%）疑为滤泡性肿瘤，3 个（6.5%）疑为恶性，28 个（60.1%）为恶性。最终组织病理学结果为良性的有 11 例（24%），DTC 为 35 例（76%），其中包括 34 例 PTC 病例和 1 例滤泡性甲状腺癌。与良性结节相比，DTC 中 CD11b(+)HLA-DR(low)HIF1a(+) MDSC (CD11b(+)MDSC) 的平均百分比分别为 14.06.2% 和 7.9 +/- 3.6% (p
Background: Establishing the preoperative diagnosis and long-term prognosis of differentiated thyroid cancer (DTC) remain challenging in some patients. Myeloid-derived suppressor cells (MDSC) are tumor-induced cells mediating immune tolerance that are detectable in the peripheral blood of cancer patients. The authors previously developed a novel clinical assay to detect the phenotypes of two human MDSC subsets in peripheral blood, and hypothesize that higher MDSC levels measured by this assay correlate positively with both malignancy and worse patient outcomes. Methods: A prospective observational pilot study was performed of patients undergoing thyroidectomy for a solitary thyroid nodule. The presence of a thyroid nodule >1cm was confirmed sonographically, and fine-needle aspiration biopsy performed prior to surgery in all cases. Peripheral blood collected preoperatively was analyzed using a novel flow cytometry-based immunoassay to detect and quantify two subsets of human MDSC. Circulating MDSC levels were compared by histopathologic diagnosis, stage, and presence of persistent disease after treatment. Results: Of 50 patients included in this study, MDSC measurement was successful in 47 (94%). One patient was found to have a concurrent cancer, leaving 46 patients for primary analysis. The cytologic diagnoses were benign in five (10.8%), atypia or follicular lesion of undetermined significance in five (10.8%), suspicious for follicular neoplasm in five (10.8%), suspicious for malignant in three (6.5%), and malignant in 28 (60.1%) of the 46 nodules. Final histopathology was benign in 11 (24%) and DTC in 35 (76%), encompassing 34 PTC cases and one follicular thyroid carcinoma. Mean percentages of CD11b(+)HLA-DR(low)HIF1a(+) MDSC (CD11b(+)MDSC) were 14.06.2% and 7.9 +/- 3.6% in DTC versus benign nodules, respectively (p