BRAF^(V600E)突变蛋白及β-catenin、cyclin D1在cN0期甲状腺微小乳头状癌中的表达及意义

Expressions of BRAF^(V600E)mutant protein,β-catenin and cyclin D1 in cN0 papillary thyroid microcarcinoma and the significance

背景与目的:虽然甲状腺微小乳头状癌(PTMC)进展缓慢,但仍常伴有颈部淋巴结转移。有研究提示,BRAF^(V600E)突变及Wnt/β-catenin信号通路中相关蛋白表达异常,可能与PTMC发生发展、颈部淋巴结转移有关。因此,本研究进一步探讨临床淋巴结阴性(cN0)PTMC病变组织中BRAF^(V600E)突变及β-catenin、cyclin D1表达及意义。方法:收集2018年3月—2021年9月120例确诊为cN0期PTMC患者的手术标本及临床病理资料,用免疫组化法检测BRAF^(V600E)突变及β-catenin、cyclin D1蛋白在标本中的表达,并分析其与患者临床病理特征的关系。结果:BRAF^(V600E)突变蛋白、β-catenin、cyclin D1蛋白表达阳性率在PTMC组织中阳性表达均明显高于癌旁组织(70%vs.31.7%、35.8%vs.20.8%、57.5%vs.34.2%,均P<0.05)。cyclin D1蛋白阳性表达与肿瘤直径有关,BRAF^(V600E)突变蛋白阳性表达与病灶数目有关,BRAF^(V600E)、β-catenin、cyclin D1蛋白阳性表达均与中央区淋巴结转移有关(均P<0.05)。结论:cN0期PTMC组织中BRAF^(V600E)突变及β-catenin、cyclin D1蛋白表达明显增强,它们的表达可能是PTMC进展及中央区淋巴结转移的重要原因。

Background and Aims:Although the progression of papillary thyroid microcarcinoma(PTMC)is relatively slow,cervical lymph node metastasis is still present.The previous study suggested that the BRAF^(V600E)mutation and the abnormal expressions of relevant proteins of the Wnt/β-catenin signaling pathway may be associated with the occurrence and development and cervical lymph node metastasis of PTMC.Therefore,this study was conducted to investigate further the BRAF^(V600E)mutation and the expressions ofβ-catenin and cyclin D1 in the clinically node-negative(cN0)PTMC tissue and the significance.Methods:The surgical specimens and clinicopathologic data of 120 patients with confirmed cN0 PTMC from March 2018 to September 2021 were collected.The BRAF^(V600E)mutation and expression levels ofβ-catenin and cyclin D1 in the tissue samples were determined by immunohistochemical staining,and their relations with the clinicopathologic characteristics of patients were analyzed.Results:The favorable expression rates of BRAF^(V600E)mutant protein,β-catenin,and cyclin D1 in PTMC tissue were significantly higher than those in tumor-adjacent tissue(70%vs.31.7%,35.8%vs.20.8%,57.5%vs.34.2%,all P<0.05).Positive expression of cyclin D1 protein was significantly related to tumor diameter,positive expression of BRAF^(V600E)mutant protein was significantly associated with the number of lesions,and positive expressions of BRAF^(V600E)mutant protein,β-catenin,and cyclin D1 were all mainly related to central lymph node metastasis(all P<0.05).Conclusion:BRAF^(V600E)mutation,β-catenin,and cyclin D1 expressions are significantly enhanced in cN0 PTMC tissue.Their expressions may be the essential reason for the progression and central lymph node metastasis of PTMC.