Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation
Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation
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DOI：
10.1111/apm.12505
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发表时间：
2016-04-01
期刊：
影响因子：
2.8
通讯作者：
Cvejic, Dubravka
中科院分区：
文献类型：
--
作者：
Bartolome, Aleksandar;Boskovic, Srdjan;Cvejic, Dubravka
SLP-2是一种具有生物学活性的蛋白质，在多种恶性肿瘤的发生、发展过程中起着重要的作用。本研究旨在分析SLP-2在甲状腺良恶性肿瘤（n = 210）中的表达模式，并探讨其与甲状腺癌临床病理参数和BRAFV 600 E突变的关系。SLP-2免疫组化表达在良性腺瘤中未检测到，在滤泡状癌和未分化癌中不存在/弱。仅在甲状腺乳头状癌（PTC）中发现的SLP-2的高表达水平，特别是在经典型中，与不良临床病理参数显著相关：淋巴结转移（p = 0.002）、甲状腺外浸润（p < 0.001）、pT状态（p < 0.001）和晚期肿瘤分期（p = 0.001）。PTC病例的BRAFV 600 E突变的额外基因分型首次揭示了SLP-2过表达与BRAF突变的存在之间的密切关系（p = 0.02），在这些病例中，淋巴结转移（70%）和甲状腺外浸润（80%）的阳性率高。SLP-2过表达与不利的临床病理特征和BRAFV 600 E突变的显著相关性表明，SLP-2可能在BRAF突变的PTC的侵袭性中起作用，并且SLP-2评估在临床上可用于识别高危PTC患者。
Stomatin-like protein 2 (SLP-2), a member of the stomatin protein family, has emerged as a potential molecular hallmark of tumor progression in several human malignancies. The aim of this study was to analyze SLP-2 expression pattern in benign and malignant thyroid tumors (n = 210) and to examine its relationship with clinicopathological parameters and BRAFV600E mutation in thyroid cancer. SLP-2 immunohistochemical expression was not detected in benign adenomas and was absent/weak in follicular and anaplastic carcinomas. High expression levels of SLP-2, found only in papillary thyroid carcinoma (PTC), particularly in the classical variant, were significantly associated with adverse clinicopathological parameters: lymph node metastasis (p = 0.002), extrathyroid invasion (p < 0.001), pT status (p < 0.001), and advanced tumor stage (p = 0.001). Additional genotyping of PTC cases for the BRAFV600E mutation revealed for the first time a close relation between SLP-2 overexpression and the presence of BRAF mutation (p = 0.02) with high positive rates of lymph node metastasis (70%) and extrathyroid invasion (80%) in these cases. The significant association of SLP-2 overexpression with unfavorable clinicopathological characteristics and BRAFV600E mutation indicates that SLP-2 may have a role in aggressiveness of BRAF-mutated PTC and that SLP-2 evaluation could be clinically useful in identification of high-risk PTC patients.