Institute for the Application of Nuclear Energy, INEP, University of Belgrade, Banatska 31b, 11080 Zemun, Belgrade, Serbia.
J Cancer Res Clin Oncol. 2010 Dec;136(12):1805-12. doi: 10.1007/s00432-010-0838-3. Epub 2010 Mar 4.
The aim of this study was to assess the clinical utility of circulating preoperative Cyfra 21.1 [soluble fragment of cytokeratin (CK) 19] and galectin-3 (gal-3) in patients with thyroid tumors, to compare their serum values with tissue expression and to analyze the prognostic significance of these markers in relation to the clinical status of postsurgical differentiated thyroid carcinoma (DTC) patients.
Concentrations of Cyfra 21.1 and gal-3 were evaluated by immunoassays in sera of 9 healthy subjects, 97 preoperative patients with diverse thyroid tumors (10 FTA, 63 PTC, 11 FTC, 5 PDTC, 4 ATC, 4 LNM) and 25 postoperative DTC patients (14 remissions and 11 metastases).
Low Cyfra 21.1 values were found in all subgroups, but with a tendency toward higher values in poorly differentiated DTC patients. Compared to the control (0.23 ng/mL), serum levels of gal-3 were significantly elevated in patients with thyroid tumors but with overlapping between adenoma (4.16 ng/mL) and carcinoma (3.85, 4.37, 4.64, 6.07 ng/mL for PTC, PDTC, ATC and LNM, respectively). The tissue expression of CK19 and gal-3 was immunohistochemically determined on 45 matched paraffin-embedded sections. Most thyroid carcinomas showed positive CK19 (27/35) and gal-3 immunostaining (31/35), while adenomas were mostly immunonegative (8/10 and 7/10, respectively). However, there was no significant correlation between their serum and tissue levels. Clinical status of postoperative DTC patients had no influence on serum concentrations of the tested markers.
While CK19 and gal-3 are accurate as tissue markers, their serum levels could not be used as reliable markers for identification of thyroid malignancy or in thyroid cancer follow-up. On the other hand, a tendency toward higher serum levels of Cyfra 21.1 in the small number of PDTC patients examined adds weight to previous reports postulating a role for cytokeratins in predicting a high degree of malignancy.
本研究旨在评估术前循环细胞角蛋白 19 可溶性片段(Cyfra 21.1)和半乳糖凝集素-3(galectin-3)在甲状腺肿瘤患者中的临床应用价值,比较其血清值与组织表达,并分析这些标志物与术后分化型甲状腺癌(DTC)患者临床状态的相关性及其预后意义。
通过免疫测定法评估 9 名健康受试者、97 名患有各种甲状腺肿瘤(10 例滤泡状甲状腺癌、63 例甲状腺乳头状癌、11 例甲状腺滤泡状癌、5 例甲状腺髓样癌、4 例未分化甲状腺癌、4 例淋巴结转移)和 25 例术后 DTC 患者(14 例缓解,11 例转移)的 Cyfra 21.1 和 gal-3 浓度。
所有亚组的 Cyfra 21.1 值均较低,但低分化 DTC 患者的 Cyfra 21.1 值有升高趋势。与对照组(0.23ng/mL)相比,甲状腺肿瘤患者的血清 gal-3 水平显著升高,但腺瘤(4.16ng/mL)与癌(甲状腺乳头状癌、甲状腺髓样癌、未分化甲状腺癌和淋巴结转移,分别为 3.85、4.37、4.64、6.07ng/mL)之间有重叠。45 例配对石蜡包埋切片采用免疫组化法测定 CK19 和 gal-3 的组织表达。大多数甲状腺癌显示 CK19(27/35)和 gal-3 免疫染色阳性(31/35),而腺瘤大多为免疫阴性(8/10 和 7/10)。然而,它们的血清和组织水平之间没有显著相关性。术后 DTC 患者的临床状态对检测标志物的血清浓度没有影响。
虽然 CK19 和 gal-3 作为组织标志物准确,但它们的血清水平不能作为识别甲状腺恶性肿瘤或甲状腺癌随访的可靠标志物。另一方面,在检查的少数 PDTC 患者中,Cyfra 21.1 的血清水平呈升高趋势,这进一步证实了细胞角蛋白在预测高度恶性方面的作用。