甲状腺乳头状癌病理亚型与临床分子 特征关系探究

Correlation of Pathological Subtypes with Clinical and Molecular Features in Papillary Thyroid Carcinoma

摘要: 目的：探讨甲状腺乳头状癌(PTC)不同病理亚型的临床病理特点及分子遗传学特征。方法：收集临沂市肿瘤医院2019年10月至2020年7月手术治疗的103例PTC患者的临床病理资料，重新阅片做出病理亚型诊断，根据病理亚型的不同分为三组，侵袭组14例，弥漫硬化组(DSV-PTC)15例，以低侵袭组74例作为对照。肿瘤组织样本DNA提取后，应用二代测序的方法对66个PTC高度相关基因进行测序，比较三组间临床病理特征的差别，分析其基因突变的特点。结果：本次研究显示，侵袭性组相较于低侵袭组更容易出现侧颈淋巴结转移和甲状腺外侵犯(P < 0.05)，结果具有统计学意义。侵袭组II、III期的占比为42.86%和14.29%，远高于低侵袭组(P < 0.05)。DSV-PTC组相较于低侵袭组肿瘤直径较小(P < 0.05)，且伴慢性淋巴性甲状腺炎的比例更高(P < 0.05)。侵袭性组均检出基因突变，其中BRAF突变率为71.43%。DSV-PTC组基因突变率为73.33%，BRAF突变率为33.33%，RET重排2例，占比13.33%。低侵袭组BRAF突变率为59.45%，BRAF联合其他基因突变12.01%。结论：侵袭性亚型PTC具有更高的侵犯、转移能力及较高基因突变率。DSV-PTC腺外侵犯和淋巴结转移不可忽视，识别侵袭性亚型对患者治疗方案选择及预后评估具有重要意义，针对基因突变可为治疗靶点选择提供潜在帮助。

Abstract: Objective: To investigate the clinicopathological and molecular genetic characteristics of papillary thyroid carcinoma subtypes (PTC). Methods: Clinicopathological data of 103 patients diagnosed with papillary thyroid carcinoma (PTC) who received surgical treatment at Linyi Cancer Hospital from October 2019 to July 2020 were collected. All histological slides were re-reviewed to confirm the diagnosis of pathological subtypes. According to the different pathological subtypes, the patients were divided into three groups: 14 cases in the invasive group, 15 cases in the diffuse sclerosing variant of PTC (DSV-PTC) group, and 74 cases in the low-invasive group, which served as the control. DNA was extracted from tumor tissue samples, and next-generation sequencing was performed to analyze 66 genes with PTC. The clinicopathological characteristics and gene mutation profiles were compared among the three groups. Results: The aggressive subtype group was more likely to show extrathyroidal invasion and lymph node metastases than low-invasive subtype group (P < 0.05). The proportions of stage II and III in the aggressive group were 42.86% and 14.29%, which were significantly higher than those in the low-invasive group (P < 0.05). The tumor diameter in DSV-PTC group was smaller than the low-invasive group (P < 0.05), and a higher proportion with chronic lymphocytic thyroiditis (P < 0.05). Gene mutations were detected in all the aggressive cases, BRAF mutation rate was 71.43%. The DSV-PTC group mutation rate was 73.33%, the BRAF mutation rate was 33.3%, 2 cases (13.33%) have RET rearrangements. The BRAF mutation rate was 59.45% in the low-invasive group, and the rate of BRAF co-mutations with other genes was 12.01%. Conclusion: Aggressive subtypes of PTC show higher invasive biologic behavior and gene mutation rates. Extrathyroidal extension and lymph node metastasis in DSV-PTC group should be required attention. Early identification of aggressive subtypes was crucial for clinical treatment and prognostic evaluation. Targeting specific gene mutations may offer potential therapeutic benefits.