超声靶向造影及弹性成像技术评价甲状腺乳头状癌BRAFV600E的表达及其促转移机制的研究

In recent years, the incidence of thyroid cancer is the fastest-growing malignancy. It grew 4.99 times by nearly 10 years in United States , 2.24 times in our country .In which it is mainly differentiated thyroid carcinoma (DTC). Since the resolution of high-frequency ultrasound to be improved , more and more thyroid cancer smaller than 1cm could be found , and it more than 50% of the total. The incidence of thyroid cancer lymph node metastasis reported in the literature tiny approximately 2.0% to 43 %. What mechanism of relatively high incidence of lymph node metastasis is ? Factors affecting lymph node metastasis have? Could ultrasound imaging as early warning for lymph node metastasis ? No related research reports. This topic through targeted ultrasound imaging and ultrasound elastography technology, research and differentiated thyroid carcinoma with lymph node metastasis and without lymph node metastasis their imaging features , the establishment of early warning systems early differentiated thyroid cancer lymph node metastasis . For easy transfer of differentiated thyroid cancer can be avoided by total thyroidectomy and neck lymph node dissection , such as excessive surgical treatment to reduce the incidence of parathyroid and laryngeal nerve damage and other anti postoperative complications . Meanwhile, the study also tiny thyroid cancer topical percutaneous radiofrequency ablation laid a theoretical foundation.

甲状腺癌是近年来发病率增长最快的恶性肿瘤。美国近10年增长了4.99倍，我国增长了2.24倍，其中主要为甲状腺乳头状癌（PTC）。由于高频超声分辨率的提高，越来越多≤1cm的甲状腺微小癌得以发现，已超过甲状腺癌总患病人数的50%。文献报告甲状腺微小癌颈部淋巴结转移的发生率约2.0%～43% 。相对高发的淋巴结转移机制是什么？影响因素有哪些？超声影像对淋巴结转移能否早期预警？尚无相关研究报道。本课题运用高分辨率超声结合靶向超声造影、弹性成像技术，与组织病理和分子病理对照研究，探索有或无淋巴结转移的甲状腺乳头状癌的超声影像特征，建立甲状腺乳头状癌早期淋巴结转移的预警系统。对于不易转移的甲状腺乳头状癌，可避免甲状腺全切和颈部淋巴结清扫等过度手术治疗，减少甲状旁腺及喉反神经损伤等术后并发症的发生。同时，该研究也为甲状腺微小乳头状癌局部经皮射频消融治疗奠定了理论基础。

大部分甲状腺乳头状癌（papillary thyroid cancer, PTC）生物学行为惰性，但仍有部分PTC易发生淋巴结转移，进而影响患者预后。因此，探讨甲状腺乳头状癌淋巴结转移的机制，提示不同临床及分子病理下PTC淋巴结转移率的影响，建立甲状腺乳头状癌淋巴结转移的预警系统，具有重要的临床意义。BRAF V600E是PTC最常见的基因突变，但对PTC的发生发展以及淋巴结转移的影响仍不明确。本研究通过分析PTC患者多模态超声征象、BRAF V600E表达与甲状腺乳头状癌淋巴结转移的相关性，探讨了甲状腺乳头状癌淋巴结转移的分子机制及影响因素，建立了甲状腺乳头状癌颈部淋巴结转移常规超声预测模型，为临床治疗方法的选择提供理论依据；同时成功构建携载 BRAF V600E 抗体的纳米微泡，在动物实验中利用超声分子影像研究 BRAF V600E阳性与阴性表达、以及不同表达量下的甲状腺乳头状癌超声功能成像特征，进一步探索了BRAF V600E在甲状腺乳头状癌细胞发生发展中的机制。