Upregulation of HGF and c-MET is Associated with Subclinical Central Lymph Node Metastasis in Papillary Thyroid Microcarcinoma
Upregulation of HGF and c-MET is Associated with Subclinical Central Lymph Node Metastasis in Papillary Thyroid Microcarcinoma
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DOI：
10.1245/s10434-014-3553-5
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发表时间：
2014-07-01
影响因子：
3.7
通讯作者：
Lim, Young Chang
中科院分区：
文献类型：
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作者：
Koo, Bon Seok;Kim, Jin Man;Lim, Young Chang
鉴定一种新的甲状腺乳头状微小癌（PTMC）亚临床淋巴结转移（SLNM）生物标志物，可以为PTMC SLNM提供重要线索。我们评估了手术切除的PTMC患者肿瘤组织中HGF和c-Met表达作为SLNM预测指标的意义，并分析了113例术前临床淋巴结阴性的手术治疗的PTMC患者中HGF和c-Met表达与SLNM的关系。此外，我们还探讨了HGF/c-Met通路激活是否促进PTC细胞的体外迁移和侵袭，免疫组化结果显示，107例（95%）和103例（91%）PTC细胞表达HGF和c-Met。肝细胞生长因子染色分布为：无染色6例，弱染色43例，中度染色55例，强染色9例。在9例HGF强染色的病例中，8例（89%）有SLNM. c-Met染色分布如下：无染色10例，弱染色39例，中度染色59例，强染色5例。在5例c-Met强染色的病例中，3例（60%）有SLNM。单因素分析显示，PTMC中SLNM的存在与HGF和c-Met的表达密切相关（P < 0.05）。多因素分析显示HGF过表达与SLNM相关（P < 0.05）。外源性HGF刺激和c-Met的组成性激活可通过增强VEGF-A的表达增强PTC细胞的迁移和侵袭能力，HGF/c-Met通路的激活与PTMC中央颈的SLNM有关。
Identification of a novel biomarker of subclinical lymph node metastasis (SLNM) in papillary thyroid microcarcinoma (PTMC) could provide important clues regarding SLNM in PTMC. We evaluated the significance of HGF and c-Met expression in surgically removed tumor tissue from PTMC patients as a predictive marker of SLNM.We analyzed the immunohistochemical relationship between HGF and c-Met expression and SLNM in 113 surgically treated PTMC patients with clinically negative nodes presurgery. In addition, we explored whether HGF/c-Met pathway activation enhanced the in vitro migration and invasion of PTC cells.Positive immunohistochemical HGF and c-Met staining was found in 107 (95 %) and 103 (91 %) cases, respectively. The HGF staining distribution was as follows: no staining in 6 cases, weak staining in 43, moderate staining in 55, and strong staining in 9. Of the nine cases with strong HGF staining, eight (89 %) had SLNM. The c-Met staining distribution was as follows: no staining in 10 cases, weak staining in 39, moderate staining in 59, and strong staining in 5. Of the five cases with strong c-Met staining, three (60 %) had SLNM. The presence of SLNM was strongly correlated with HGF and c-Met expression in PTMC in a univariate analysis (P < 0.05). HGF overexpression was also associated with SLNM in a multivariate analysis (P < 0.05). Stimulation with exogenous HGF and constitutive activation of c-Met enhanced the migration and invasion of PTC cells in vitro by enhancing VEGF-A expression.HGF/c-Met pathway activation is associated with SLNM of the central neck in PTMC.