甲状腺髓样癌分子分型及治疗.pptxVIP

甲状腺髓样癌分子分型及治疗第1页/共38页 概况Histologic subtypes of thyroid cancer ①Papillary: approximately 80% of all thyroid malignancies; ②Follicular and Hürthle: approximately 11%; ③Medullary: less than 5%-8% ;④Anaplastic: less than 2%.  第2页/共38页 Introduction Medullary thyroid cancer (MTC)①Sporadic MTC: approximately 75%; 50% somatic RET mutations (p.M918T) -predict a poor prognosis ②Hereditary MTC: approximately 25%; 98% Germline RET mutations, MEN 2A (~95%) and MEN 2B (~5%)  Arises from the neural crest-derived, calcitonin-secreting, parafollicular C cells of the thyroid gland 第3页/共38页 Introduction ①Sporadic MTC: a solitary and unilateral or a palpable cervical lymph node ②Hereditary MTC: multicentric and bilateral the upper to middle parts of the thyroid lobes  第4页/共38页 Introduction Involvement of cervical lymph nodes is an early and common manifestation in the clinical course of the disease, with 35% to 50% or more, another 10% to 15% may have distant metastases at the time of initial presentation; Distant metastatic spread of MTC frequently involves the mediastinal nodes, lung, liver (90%), and bones.第5页/共38页 p.C611YMEN2A第6页/共38页 Molecular Aberrations (overexpression )① RET mutations ② VEGFR-2 ③ MET ④ EGFR⑤ FGFR⑥ RAS (sMTC---56% KRAS+;12%HRAS)(Mutations in RAS appear to be mutually exclusive of RET abnormalities)Somatic RET mutations第7页/共38页 Molecular pathways ① PI3K/Akt/mTOR ② MAPK ③ JNK ④ RAS/ERKPlay critical roles in regulating cell proliferation, differentiation, motility, apoptosis, and survival 第8页/共38页 Diagnosis and Monitoring① FNA,US and CT, MRI or ECT (Ct 500 pg/mL);② DNA analysis for the RET germline mutation ATA-2015, ETA-2013, NCCN-2017 Guidelines recommend ③ The MTC specimen is positively stained for Ct, chromogranin A, and CEA or Congo Red. 第9页/共38页 Diagnosis and