Department of Endocrinology, Ninth Affiliated Hospital of Guangxi Medical University, Beihai - China.
Int J Biol Markers. 2010 Jan-Mar;25(1):38-45. doi: 10.1177/172460081002500106.
Early diagnosis and treatment of thyroid cancers are critical for better prognosis and better survival rates. The purpose of this study was to identify potential diagnostic markers for papillary thyroid carcinomas with distant metastasis. Fifty-eight papillary thyroid tumor specimens (27 papillary thyroid carcinomas with distant metastasis and 31 without metastasis) were examined, and protein expression of pituitary tumor-transforming gene (PTTG), E-cadherin, p27kip1, vascular endothelial growth factor (VEGF)-C, metalloproteinase (MMP) 2, MMP9, chemokine receptor CXCR4, and basic fibroblast growth factor (bFGF) in these tumors was assessed by immunohistochemistry. The clinicopathological variables with diagnostic significance were determined by multivariate analysis, and their diagnostic values were evaluated by ROC curve analysis. PTTG, VEGF-C, MMP2, MMP9, CXCR4, and bFGF were overexpressed in metastatic papillary thyroid carcinomas, whereas p27kip1 expression was elevated only in carcinomas lacking metastasis. Multiple-factor binary ordinal logistic regression analysis revealed that PTTG, VEGF-C, MMP2, and bFGF were independently related to biological metastatic behavior in thyroid tumors, suggesting their potential use as biomarkers. ROC curve analysis showed that among these four proteins, VEGF-C and bFGF were the best diagnostic biomarkers. A VEGF-C and bFGF cluster was the most useful factor for the differential diagnosis between metastatic and non-metastatic papillary thyroid cancers. Thus, the combined use of VEGF-C and bFGF as biomarkers may improve the diagnostic accuracy of papillary thyroid carcinoma and may be useful in multimodal screening programs for the clinical diagnosis of papillary thyroid carcinoma and early detection of papillary thyroid carcinoma with distant metastasis.
早期诊断和治疗甲状腺癌对于改善预后和提高生存率至关重要。本研究旨在确定具有远处转移的甲状腺乳头状癌的潜在诊断标志物。检查了 58 例甲状腺乳头状肿瘤标本（27 例甲状腺乳头状癌伴远处转移，31 例无转移），通过免疫组织化学方法评估这些肿瘤中垂体肿瘤转化基因（PTTG）、E-钙黏蛋白、p27kip1、血管内皮生长因子（VEGF）-C、基质金属蛋白酶（MMP）2、MMP9、趋化因子受体 CXCR4 和碱性成纤维细胞生长因子（bFGF）的蛋白表达。通过多变量分析确定具有诊断意义的临床病理变量，并通过 ROC 曲线分析评估其诊断价值。转移性甲状腺乳头状癌中 PTTG、VEGF-C、MMP2、MMP9、CXCR4 和 bFGF 过表达，而 p27kip1 仅在无转移的癌中表达上调。多因素二项有序逻辑回归分析显示，PTTG、VEGF-C、MMP2 和 bFGF 与甲状腺肿瘤的生物学转移行为独立相关，提示它们可能作为生物标志物使用。ROC 曲线分析表明，在这四种蛋白中，VEGF-C 和 bFGF 是最佳的诊断生物标志物。VEGF-C 和 bFGF 聚类是鉴别转移性和非转移性甲状腺乳头状癌的最有用因素。因此，联合使用 VEGF-C 和 bFGF 作为生物标志物可能提高甲状腺乳头状癌的诊断准确性，并可能有助于甲状腺乳头状癌的多模式筛查计划和远处转移甲状腺乳头状癌的早期发现。
