Department of Otolaryngology-Head and Neck Surgery/Surgical Oncology, University Health Network, Toronto, ON, Canada.
Endocr Pathol. 2012 Dec;23(4):232-42. doi: 10.1007/s12022-012-9225-8.
Unlike papillary thyroid carcinoma, medullary thyroid carcinoma is insensitive to adjuvant treatment with radioactive iodine. The clinical management of patients with advanced or metastatic disease remains challenging since no effective systemic adjuvant therapy is available. We aimed to identify markers of aggressive disease and novel drugable protein targets that would provide systemic adjuvant treatment for patients with advanced medullary thyroid carcinoma. We therefore examined morphologic features of aggressive behavior and the expression of 41 proteins involved in apoptosis, cell cycle, angiogenesis, inflammation, cell adhesion, tumor-specific markers, and WNT, SHH, and AKT pathways using tissue microarray from 23 patients with medullary thyroid carcinoma. Protein expression was determined using computerized image analysis software. Statistical analysis was carried out to correlate clinical data with the average score for each marker. Angioinvasion proved to be the most reliable predictor of disease recurrence and death. The rate of angioinvasion was 43 %. All angioinvasive medullary thyroid carcinomas had locoregional and/or distant metastasis; 60 % of angioinvasive medullary thyroid carcinomas developed distant metastasis. We identified expression of several potentially important protein targets such as COX-1/2, Bcl-2a, Gst-π, Gli-1, Gli-2, Gli-3, and Bmi-1 that may be therapeutically targeted in medullary thyroid carcinoma. More importantly, the immunohistochemical profile of SSTRs in medullary thyroid carcinoma may also have clinical relevance for the administration of peptide receptor radionuclide treatment. Successful outcome of clinical trials directed against these novel targets would provide much needed systemic adjuvant treatment for patients with advanced medullary thyroid carcinoma, and our data suggest the possibility of stratifying patients who are likely to require adjuvant therapy before their burden of disease precludes successful therapeutic effect.
不像甲状腺乳头状癌，甲状腺髓样癌对放射性碘的辅助治疗不敏感。由于没有有效的全身辅助治疗方法，晚期或转移性疾病患者的临床管理仍然具有挑战性。我们旨在确定侵袭性疾病的标志物和新的可用药蛋白靶点，为晚期甲状腺髓样癌患者提供全身辅助治疗。因此，我们使用 23 例甲状腺髓样癌患者的组织微阵列检查了侵袭性行为的形态特征以及涉及凋亡、细胞周期、血管生成、炎症、细胞黏附、肿瘤特异性标志物和 WNT、SHH 和 AKT 途径的 41 种蛋白的表达。使用计算机图像分析软件确定蛋白质表达。进行统计分析以将临床数据与每个标志物的平均评分相关联。血管侵袭被证明是疾病复发和死亡的最可靠预测因子。血管侵袭率为 43%。所有血管侵袭性甲状腺髓样癌均有局部和/或远处转移；60%的血管侵袭性甲状腺髓样癌发生远处转移。我们发现了几种潜在重要的蛋白靶点的表达，如 COX-1/2、Bcl-2a、Gst-π、Gli-1、Gli-2、Gli-3 和 Bmi-1，这些靶点可能是甲状腺髓样癌的治疗靶点。更重要的是，甲状腺髓样癌中 SSTR 的免疫组织化学特征也可能对肽受体放射性核素治疗的管理具有临床意义。针对这些新靶点的临床试验取得成功将为晚期甲状腺髓样癌患者提供急需的全身辅助治疗，并且我们的数据表明，在疾病负担排除成功治疗效果之前，对可能需要辅助治疗的患者进行分层的可能性。
