A High-Throughput Proteomic Approach Provides Distinct Signatures for Thyroid Cancer Behavior
A High-Throughput Proteomic Approach Provides Distinct Signatures for Thyroid Cancer Behavior
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DOI：
10.1158/1078-0432.ccr-10-2837
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发表时间：
2011-04-15
影响因子：
11.5
通讯作者：
Asa, Sylvia L.
中科院分区：
文献类型：
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作者：
Cheng, Sonia;Serra, Stefano;Asa, Sylvia L.
目的：高分化甲状腺癌（WDTC）是最常见的内分泌肿瘤。该疾病治疗的主要挑战之一是区分可通过手术切除病变的低风险患者与需要更广泛方法（包括甲状腺全切除术和放射性碘消融）的高复发可能性患者。实验设计：构建了包含410例WDTC的组织微阵列（TMA），并对以下特征进行了风险评估：甲状腺外扩张、淋巴结转移和血管侵犯。检查的变量包括形态学分类、候选遗传和蛋白质组学生物标志物。结果：与野生型（WT）病例相比，BRAF （Raf激酶B型）突变携带者发生侵袭的风险增加。然而，当形态学分类时，与滤泡变异型甲状腺乳头状癌（FVPTC）相比，典型甲状腺乳头状癌（PTC）表现出更高的侵袭性特征风险；在这些形态亚组中，BRAF突变状态不能提供独立的风险估计。膜状半乳糖凝集素-3 （Gal3）、HBME-1、CK19和核状Gal3的染色强度在统计学上被证实是攻击行为的标志。雌激素受体β (ER β)在具有侵袭性行为的病变中过度表达。这些生物标志物的效用在FVPTC中仍然具有统计学意义。相比之下，另一组生物标志物在经典PTC中被证明是有效的，其中cyclin D1的上调、p27的缺失和ERb的过表达与侵袭行为相关。结论：不同的蛋白质组学特征验证了经典和FVPTC的区别，为预测甲状腺癌行为和患者分层提供了实用的临床机制。临床癌症研究；17日(8);2385 - 94。(c) 2011年aacr。
Purpose: Well-differentiated thyroid cancer (WDTC) is the most frequent form of endocrine neoplasia. One of the main challenges in the management of this disease is distinguishing low-risk patients who can be treated by surgical resection of the lesion from those with a high likelihood of recurrence who need a more extensive approach, including total thyroidectomy and radioiodine ablation.Experimental Design: A tissue microarray (TMA) comprising 410 cases of WDTC was constructed with risk estimates for the following features: extrathyroidal extension, lymph node metastases, and vascular invasion. The variables examined were morphologic classification, candidate genetic, and proteomic biomarkers.Results: BRAF (Raf kinase type B) mutant carriers showed increased risk of developing invasion compared with wild-type (WT) cases. However, when classified morphologically, classic papillary thyroid carcinomas (PTC) showed much higher risk estimates for invasive features compared with follicular variant PTCs (FVPTC); within these morphologic subgroups, BRAF mutational status did not provide independent risk estimates. Staining intensities for membranous galectin-3 (Gal3), HBME-1, and CK19 and nuclear Gal3 were statistically validated as markers of aggressive behavior. Estrogen receptor beta (ER beta) was overexpressed in lesions with invasive behavior. The utility of these biomarkers remained statistically significant in the FVPTC. In contrast, a different set of biomarkers proved effective in classic PTC where upregulation of cyclin D1, loss of p27, and overexpression of ERb were associated with invasive behavior.Conclusion: Different proteomic signatures validate the distinction of classic and FVPTC and provide a practical clinical mechanism to predict the thyroid cancer behavior and stratify patients for clinical management. Clin Cancer Res; 17(8); 2385-94. (C) 2011 AACR.