Choden Sonam, Keelawat Somboon, Jung Chan Kwon, Bychkov Andrey
Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Gland Surg. 2020 Oct;9(5):1867-1877. doi: 10.21037/gs-20-388.
Papillary thyroid carcinoma (PTC) accounts for the majority of diagnoses of thyroid carcinoma. mutation is the most common genetic alteration in PTC, which has diagnostic and prognostic significance. The rate of mutation in PTC from Thailand has not been reported. Our purpose was to estimate the prevalence of mutation in a large institutional series using an affordable approach, which combined mutation-specific immunohistochemistry (IHC) with VE1 antibody and tissue microarray (TMA).
A total of 476 PTC cases plotted on TMA were employed for determining the mutation status in this study. The cancer tissue of initial 100 cases (pilot study) were analyzed for mutation by using both direct sequencing and VE1 immunostaining. For the subsequent PTC cases, VE1 IHC was used as an alternative to direct sequencing for the detection of mutation. Univariate and multivariate analyses were done to determine the association of clinicopathological variables with mutation.
In the pilot study, VE1 IHC showed excellent analytical performance (κ=0.884) for detecting mutation in PTC TMA as compared to direct sequencing. The prevalence of in the whole cohort was 60.9% by using VE1 IHC. The mutation was commonly seen in tall cell (92.9%) and classic (70.2%) variants of PTC. Multivariate analysis (P<0.05) showed association of with histological type of tumor, extrathyroidal extension, and absence of Hashimoto's thyroiditis.
In conclusion, mutation was detected in 60.9% of Thai PTC and it was associated with several aggressive clinicopathological variables of thyroid cancer. VE1 IHC proved as a reliable method able to replace direct sequencing for detection of the mutation. A combination of mutation-specific IHC and TMA allows conducting large cohort studies more labor-saving and cost-efficiently.
甲状腺乳头状癌（PTC）占甲状腺癌诊断的大多数。 突变是PTC中最常见的基因改变，具有诊断和预后意义。泰国PTC中 突变的发生率尚未见报道。我们的目的是使用一种经济实惠的方法估计大型机构系列中 突变的患病率，该方法将突变特异性免疫组织化学（IHC）与VE1抗体和组织微阵列（TMA）相结合。
本研究共使用476例绘制在TMA上的PTC病例来确定 突变状态。最初100例病例（初步研究）的癌组织通过直接测序和VE1免疫染色分析 突变。对于后续的PTC病例，VE1 IHC用作检测 突变的直接测序替代方法。进行单变量和多变量分析以确定临床病理变量与 突变的关联。
在初步研究中，与直接测序相比，VE1 IHC在检测PTC TMA中的 突变方面表现出优异的分析性能（κ=0.884）。使用VE1 IHC，整个队列中的 患病率为60.9%。 突变常见于PTC的高细胞（92.9%）和经典（70.2%）变体中。多变量分析（P<0.05）显示 与肿瘤组织学类型、甲状腺外扩展和无桥本甲状腺炎有关。
总之，在60.9%的泰国PTC中检测到 突变，并且它与甲状腺癌的几个侵袭性临床病理变量相关。VE1 IHC被证明是一种可靠的方法，能够替代直接测序来检测 突变。突变特异性IHC和TMA的组合使得能够更省力且经济高效地进行大型队列研究。
