Genetic alterations in papillary thyroid cancer: clinicopathological correlations and diagnostic implications.

IF 2.2 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Enaam Mohammed Ali Junainah
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引用次数: 0

Abstract

Introduction: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, encompassing distinct histological variants and a wide spectrum of clinical behaviors. Advances in molecular diagnostics have identified key genetic alterations - particularly BRAF V600E, RAS mutations, RET/PTC fusions, and TERT promoter mutations - that are strongly linked to tumor aggressiveness and prognosis. This study aimed to determine the prevalence of these alterations and evaluate their clinicopathological significance in a Saudi Arabian patient cohort.

Materials and methods: A retrospective analysis was conducted on 114 formalin-fixed paraffin-embedded (FFPE) PTC samples diagnosed between 2019 and 2023. Targeted next-generation sequencing (NGS) was used to detect BRAF, NRAS, KRAS, HRAS, RET/PTC fusions, and TERT promoter mutations. Immunohistochemistry (IHC) for BRAF V600E, TTF-1, CK19, HBME-1, and galectin-3 was performed using automated staining systems. Associations between genetic alterations and clinicopathological parameters - including tumor size, histological subtype, lymph node metastasis, and extrathyroidal extension - were analyzed statistically.

Results: BRAF V600E mutations were identified in 39.5% of cases and were significantly associated with larger tumor size (P = 0.01), extrathyroidal extension (P = 0.04), and lymph node metastasis (P = 0.03). RET/PTC fusions were detected in 15.8% of patients, predominantly younger individuals, and correlated with multifocal tumors and lymphovascular invasion. RAS mutations (19.3%) were more frequent in the follicular variant but showed no significant association with adverse features. TERT promoter mutations were present in 10.5% of cases, significantly correlating with older age and advanced tumor stage. IHC profiles demonstrated strong concordance with molecular findings.

Conclusions: In this Middle Eastern cohort of PTC patients, BRAF V600E and TERT promoter mutations were significantly associated with aggressive clinicopathological features, while RET/PTC fusions and RAS mutations demonstrated distinct demographic and histological distributions. The integration of NGS and IHC enhanced diagnostic accuracy and supports personalized risk stratification in PTC management.

甲状腺乳头状癌的基因改变:临床病理相关性和诊断意义。
简介:甲状腺乳头状癌(PTC)是最常见的甲状腺恶性肿瘤,包括不同的组织学变异和广泛的临床行为。分子诊断技术的进步已经确定了与肿瘤侵袭性和预后密切相关的关键遗传改变,特别是BRAF V600E、RAS突变、RET/PTC融合和TERT启动子突变。本研究旨在确定这些改变的患病率,并评估其在沙特阿拉伯患者队列中的临床病理意义。材料与方法:回顾性分析2019 - 2023年诊断的114份福尔马林固定石蜡包埋(FFPE) PTC样品。靶向下一代测序(NGS)用于检测BRAF、NRAS、KRAS、HRAS、RET/PTC融合和TERT启动子突变。使用自动染色系统对BRAF V600E、TTF-1、CK19、HBME-1和半乳糖凝集素-3进行免疫组化(IHC)检测。基因改变与临床病理参数(包括肿瘤大小、组织学亚型、淋巴结转移和甲状腺外扩张)之间的关系进行统计学分析。结果:BRAF V600E突变发生率为39.5%,与肿瘤体积增大(P = 0.01)、甲状腺外扩张(P = 0.04)、淋巴结转移(P = 0.03)相关。15.8%的患者(主要是年轻人)检测到RET/PTC融合,并与多灶性肿瘤和淋巴血管侵袭相关。RAS突变(19.3%)在滤泡型变异中更为常见,但与不良特征无显著相关性。10.5%的病例中存在TERT启动子突变,与年龄和肿瘤分期显著相关。免疫组化谱显示了与分子发现的强烈一致性。结论:在中东PTC患者队列中,BRAF V600E和TERT启动子突变与侵袭性临床病理特征显著相关,而RET/PTC融合和RAS突变表现出不同的人口统计学和组织学分布。NGS和IHC的整合提高了诊断的准确性,并支持PTC管理中的个性化风险分层。
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来源期刊
Folia histochemica et cytobiologica
Folia histochemica et cytobiologica 生物-生化与分子生物学
CiteScore
2.80
自引率
6.70%
发文量
56
审稿时长
6-12 weeks
期刊介绍: "Folia Histochemica et Cytobiologica" is an international, English-language journal publishing articles in the areas of histochemistry, cytochemistry and cell & tissue biology. "Folia Histochemica et Cytobiologica" was established in 1963 under the title: ‘Folia Histochemica et Cytochemica’ by the Polish Histochemical and Cytochemical Society as a journal devoted to the rapidly developing fields of histochemistry and cytochemistry. In 1984, the profile of the journal was broadened to accommodate papers dealing with cell and tissue biology, and the title was accordingly changed to "Folia Histochemica et Cytobiologica". "Folia Histochemica et Cytobiologica" is published quarterly, one volume a year, by the Polish Histochemical and Cytochemical Society.
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