【作者】 黄海燕；

【导师】 严佶祺；

【作者基本信息】 上海交通大学 ， 外科学（专业学位）， 2019， 硕士

【摘要】 甲状腺乳头状癌(Papillary thyroid carcinoma,PTC)虽总体预后良好,但伴颈部淋巴结多发转移甚至远处转移的病例并不少见。近年来,多项研究发现PTC中不同的基因突变与其侵袭性、预后等相关,但目前临床意义尚未完全明确。得益于二代基因测序技术的发展,目前临床上高通量的多基因快速平行测序已成为可能。本研究对2017年8月至2018年1月于我院行手术治疗且手术标本行二代基因测序的305例PTC病人进行回顾性分析,收集病人的基因测序结果及各项临床病理数据,分析不同基因突变与各项临床病理特征、肿瘤分期和复发风险的相关性及PTC侵袭性的相关因素。结果显示,BRAF突变存在于大部分(68.85%)PTC,与肿瘤最大径超过10 mm呈独立正相关,与合并桥本氏甲状腺炎呈独立负相关,而与性别、年龄、身体质量指数、术前血清25-OH VitD水平、肿瘤多灶性、病灶数目、淋巴结转移情况、转移数目、TNM分期、复发风险分层各项指标无统计学关联。BRAF V600E突变合并其他基因突变对肿瘤侵袭性的影响无统计学意义。男性、较小的年龄、较大的肿瘤、较多的病灶数为PTC侵袭性的独立危险因素,BRAF突变不是PTC侵袭性的危险因素。这提示了在判断PTC肿瘤侵袭性及评价预后方面,目前临床病理特征仍然比基因等分子标志物的指标更为可靠和重要,可能需要寻找新的分子标志物以进行联合评价。更多还原

【Abstract】 Despite the overall good prognosis of papillary thyroid carcinoma（PTC）,PTC with multiple lymph node metastases or even distant metastasis is not a rare clinical event.In recent years,several studies have found that different gene mutations in PTC might be related to the tumor invasiveness and prognosis.However,the clinical significance still remains unclear.Thanks to the development of next-generation sequencing technology,rapid high-throughput multi-gene parallel sequencing are now clinically possible.This study retrospectively analyzed 305 PTC patients who underwent surgical treatment in our hospital between August 2017 and January 2018 with their surgical specimens undergone next-generation gene sequencing.The patients’gene sequencing results and clinicopathological data were collected and the relations between different gene mutations and various clinicopathological features,tumor stage and risk of recurrence were analyzed.Risk factors related to the tumor invasiveness were also studied.Results show that BRAF^V600E mutation existed in most（68.85%）PTCs,and was found to be associated with tumors larger than 10 mm and those without coexisting Hashimoto’s thyroiditis.However,the mutation was found no significant correlations with gender,age,preoperative serum25-OH VitD levels,tumor multifocality,number of lesions,lymph node metastasis or number of metastatic lymph nodes,TNM stage,or recurrence risk stratification.There was no statistically significant effect of BRAF^V600E600E mutation combined with other gene mutations on tumor invasiveness.Males,younger age,larger tumors,and more lesions were independent risk factors for PTC invasiveness,while BRAF mutation was not.Thus it suggests that currently,clinicopathological features are still more important and more reliable in evaluation of PTC invasiveness and prognosis than molecular markers like genes.New molecular markers should be needed to make a combined evaluation for more accurate results.更多还原