Yamakawa M, Yamada K, Tsuge T, Ohrui H, Ogata T, Dobashi M, Imai Y
Second Department of Pathology, Yamagata University School of Medicine, Japan.
Cancer. 1994 Jun 1;73(11):2808-17. doi: 10.1002/1097-0142(19940601)73:11<2808::aid-cncr2820731125>3.0.co;2-p.
Clinical and experimental studies have suggested that complement activation may play a role in tumor cytotoxicity. Little information is available concerning the presence of complement activation and the localization of complement-regulatory factors in cells or tissues of malignant tumors. The aim of the present study was to examine, using immunohistochemistry and immunoelectron microscopy, whether the complement system is activated in tissues of thyroid carcinoma and whether thyroid carcinoma cells are protected from cell lysis by in situ complement activation.
Fresh tissues were obtained by thyroidectomy from 15 patients with papillary carcinomas, 7 with follicular carcinomas, and 5 with follicular adenomas. In addition, five specimens of histologically normal thyroid tissue and five specimens of chronically inflamed tissue adjacent to thyroid neoplasms were studied. Immunohistochemical and immunoelectron microscopic localization of complement components, C3d and C5b-9, and the complement-regulatory factors, such as s-protein, decay-accelerating factor (CD55), membrane cofactor protein (CD46), complement receptor types 1 (CD35) and 2 (CD21), and protectin (CD59), were examined in these tissues.
The staining patterns of C3d, C5b-9, and s-protein were positive and homogeneous in the nonneoplastic and most neoplastic thyroid tissues. Immunoelectron microscopy showed these antigens were localized mainly on the subepithelial and vascular basement membranes and attached to the cell surface of thyroid follicular cells. Decay-accelerating factor (CD55) was present homogeneously on the basement membranes, on the basal cell border of the thyroid follicular cells, and often on the luminal surface of carcinoma cells. Both membrane cofactor protein (CD46) and protectin (CD59) were expressed strongly on the cell surface of almost all benign and malignant thyroid follicular cells. Membrane cofactor protein was expressed on both the basal and lateral membrane, showing cell-to-cell interaction, but rarely on the luminal surface, whereas protectin was expressed strongly on the luminal surface and often on the basal cell border but rarely on the lateral membrane. Neither complement receptor type 1 (CD35) nor complement receptor type 2 (CD21) was expressed on any thyroid follicular cells.
The present study confirmed the presence of complement activation with subsequent deposition of C3d and C5b-9 complexes in thyroid carcinomas. It also indicated that thyroid carcinoma cells are protected from cell lysis because of complement activation in multiple phases by complete coverage of the entire cell membrane surface with complement-regulatory factors. These findings were similar to those found in nonneoplastic thyroid follicular cells.
临床和实验研究表明，补体激活可能在肿瘤细胞毒性中起作用。关于恶性肿瘤细胞或组织中补体激活的存在以及补体调节因子的定位，目前所知甚少。本研究的目的是利用免疫组织化学和免疫电子显微镜检查甲状腺癌组织中补体系统是否被激活，以及甲状腺癌细胞是否因原位补体激活而免受细胞溶解。
通过甲状腺切除术从15例乳头状癌、7例滤泡状癌和5例滤泡性腺瘤患者获取新鲜组织。此外，还研究了5份组织学正常的甲状腺组织标本和5份甲状腺肿瘤旁慢性炎症组织标本。检测这些组织中补体成分C3d和C5b-9以及补体调节因子，如s蛋白、衰变加速因子（CD55）、膜辅助蛋白（CD46）、补体受体1型（CD35）和2型（CD21）以及保护素（CD59）的免疫组织化学和免疫电子显微镜定位。
在非肿瘤性和大多数肿瘤性甲状腺组织中，C3d、C5b-9和s蛋白的染色模式呈阳性且均匀。免疫电子显微镜显示这些抗原主要定位于上皮下和血管基底膜，并附着于甲状腺滤泡细胞的细胞表面。衰变加速因子（CD55）均匀存在于基底膜、甲状腺滤泡细胞的基底细胞边界，且常存在于癌细胞的腔面。膜辅助蛋白（CD46）和保护素（CD59）在几乎所有良性和恶性甲状腺滤泡细胞的细胞表面均强烈表达。膜辅助蛋白在基底膜和侧膜均有表达，显示细胞间相互作用，但在腔面很少表达，而保护素在腔面强烈表达，且常位于基底细胞边界，但在侧膜很少表达。任何甲状腺滤泡细胞均未表达补体受体1型（CD35）和补体受体2型（CD21）。
本研究证实甲状腺癌中存在补体激活，并随后有C3d和C5b-9复合物沉积。研究还表明，由于补体调节因子完全覆盖整个细胞膜表面，甲状腺癌细胞在多个阶段因补体激活而免受细胞溶解。这些发现与非肿瘤性甲状腺滤泡细胞中的发现相似。
