Gupta S, Patel A, Folstad A, Fenton C, Dinauer C A, Tuttle R M, Conran R, Francis G L
Department of Pediatrics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
J Clin Endocrinol Metab. 2001 Mar;86(3):1346-54. doi: 10.1210/jcem.86.3.7310.
An immune response directed against thyroid cancer might be important in preventing metastasis and recurrence. This idea is supported by previous observations showing that adults with autoimmune thyroiditis or lymphocytic infiltration surrounding papillary thyroid carcinoma (PTC) have improved disease-free survival. The long-term outcome for differentiated thyroid cancer is even more favorable for children and young adults. If the immune response is important, we hypothesized that tumor-associated lymphocytes with a high proliferation index would be found in thyroid cancers from children and young adults and would be associated with improved disease-free survival. Using immunohistochemistry, we examined 39 childhood PTC, 9 follicular thyroid carcinomas, 2 medullary thyroid carcinomas, 11 benign thyroid lesions, and 2 normal thyroid glands for the presence of lymphocytes (leukocyte common antigen) and lymphocyte proliferation (proliferating cell nuclear antigen, Ki-67). The majority of PTC (65%) and follicular thyroid carcinomas (75%) from children and young adults contained lymphocytes in the immediate vicinity of thyroid cancers, but only 7 (18%) patients with PTC also had a diagnosis of autoimmune thyroiditis. Disease-free survival did not correlate with the presence or number of lymphocytes per high power field. In contrast, disease-free survival was significantly improved (P = 0.01) for thyroid cancers with the greatest number of Ki-67-positive lymphocytes per high power field. The number of lymphocytes per high powered field was greater for multifocal PTC (P: = 0.023), and the number of proliferating lymphocytes was greatest for PTC with regional lymph node involvement (30.5 +/- 12.3 vs. 6.8 +/- 5.0; P = 0.047). We conclude that proliferation of tumor-associated lymphocytes is associated with improved disease-free survival for children and young adults with thyroid cancer.
针对甲状腺癌的免疫反应可能在预防转移和复发方面具有重要作用。先前的观察结果支持了这一观点，即患有自身免疫性甲状腺炎或乳头状甲状腺癌（PTC）周围有淋巴细胞浸润的成年人无病生存期得到改善。分化型甲状腺癌在儿童和年轻成年人中的长期预后甚至更有利。如果免疫反应很重要，我们推测在儿童和年轻成年人的甲状腺癌中会发现具有高增殖指数的肿瘤相关淋巴细胞，并且这与无病生存期的改善有关。我们采用免疫组织化学方法，检测了39例儿童PTC、9例滤泡状甲状腺癌、2例髓样甲状腺癌、11例良性甲状腺病变以及2个正常甲状腺组织中淋巴细胞（白细胞共同抗原）的存在情况和淋巴细胞增殖情况（增殖细胞核抗原，Ki-67）。儿童和年轻成年人的大多数PTC（65%）和滤泡状甲状腺癌（75%）在甲状腺癌紧邻区域含有淋巴细胞，但只有7例（18%）PTC患者同时诊断为自身免疫性甲状腺炎。无病生存期与每高倍视野中淋巴细胞的存在或数量无关。相比之下，每高倍视野中Ki-67阳性淋巴细胞数量最多的甲状腺癌患者无病生存期显著改善（P = 0.01）。多灶性PTC每高倍视野中的淋巴细胞数量更多（P = 0.023），区域淋巴结受累的PTC中增殖淋巴细胞数量最多（30.5±12.3对6.8±5.0；P = 0.047）。我们得出结论，肿瘤相关淋巴细胞的增殖与儿童和年轻成年人甲状腺癌患者无病生存期的改善有关。
