Molecular Profiling of Follicular Variant of Papillary Thyroid Cancer Reveals Low-Risk Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: A Paradigm Shift to Reduce Aggressive Treatment of Indolent Tumors.
Molecular Profiling of Follicular Variant of Papillary Thyroid Cancer Reveals Low-Risk Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: A Paradigm Shift to Reduce Aggressive Treatment of Indolent Tumors.
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DOI：
10.4103/ijem.ijem_86_18
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发表时间：
2018-05
影响因子：
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通讯作者：
Gupta SK
中科院分区：
文献类型：
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作者：
George N;Agarwal A;Kumari N;Agarwal S;Krisnani N;Gupta SK
包膜型甲状腺乳头状癌（EFVPTC）被重新分类为具有乳头状核特征的非侵袭性甲状腺滤泡性肿瘤（NIFTP）和侵袭性EFVPTC。NIFTP被认为是一种低风险肿瘤。因此，滤泡型甲状腺乳头状癌（FVPTC）目前有两种不同的组织病理学亚型-侵袭性EFVPTC和浸润性/弥漫性FVPTC。这些群体的分子特征仍不清楚。通过限制性片段长度形态聚合酶链反应（PCR）和桑格测序，对30例FVPTC（10例NIFFT、12例侵袭性EFVPTC和8例浸润性/弥漫性变体）进行了审查和BRAF和RAS突变筛查。采用实时荧光定量PCR分析碘代谢相关基因的mRNA表达水平。突变状态和mRNA表达水平与临床病理特征相关。所有10个NIFTP都具有优势卵泡模式。NRAS突变1例，BRAF突变0例。所有侵袭性EFVPTC均有包膜和/或淋巴管浸润，4/12例有淋巴结转移。BRAF和NRAS分别见于3例侵袭性FVPTC。所有8例浸润性/弥漫性FVPTC均表现为浸润至邻近甲状腺实质和淋巴结转移。NIFTP组织中钠碘转运体（NIS）的表达与正常甲状腺组织相似，而侵袭性和浸润/弥漫性FVPTC组织中NIS表达下调。我们的研究支持了NIFTP可以被认为是低风险滤泡性甲状腺肿瘤的论点。携带BRAF突变的那些肿瘤可以提供完全甲状腺切除术，因为它们显示NIS基因表达降低，这赋予失去放射性碘亲合力和肿瘤进一步复发的趋势。
Encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) has been reclassified into noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and invasive EFVPTC. NIFTP is considered a low-risk neoplasm. Therefore, follicular variant of papillary thyroid cancer (FVPTC) presently has two distinct histopathological subtypes – invasive EFVPTC and infiltrative/diffuse FVPTC. Molecular characteristics of these groups remain unclear. Thirty FVPTCs (10 NIFTPs, 12 invasive EFVPTCs, and 8 infiltrative/diffuse variants) were reviewed and screened for BRAF and RAS mutations by restriction fragment length morphism-polymerase chain reaction (PCR) and Sanger sequencing. The mRNA expression levels of iodine-metabolizing genes were analyzed using real-time PCR. The mutations status and mRNA expression levels were correlated with clinicopathological features. All 10 NIFTPs had predominant follicular pattern. One case showed NRAS mutation, whereas none showed BRAF mutation. All invasive EFVPTC had capsular and/or lymphovascular invasion and 4/12 showed lymph node metastasis. BRAF and NRAS were seen in three cases each of invasive FVPTC. All eight infiltrating/diffuse FVPTCs showed infiltration into adjacent thyroid parenchyma and lymph node metastasis. BRAF mutation was observed in 62.5% of cases; however, no NRAS mutation was found. Sodium iodide symporter (NIS) expressions in NIFTP were similar to that of normal thyroid tissue, whereas it was downregulated in invasive and infiltrative/diffuse FVPTC. Our study supports the argument that NIFTP can be considered as low-risk follicular thyroid neoplasm. Those tumors that harbor BRAF mutations may be offered a complete thyroidectomy because they show decreased expression of NIS gene which confers a tendency to lose radioactive iodine avidity and further recurrence of the tumor.