PROTECTION OF THYROID-CANCER CELLS BY COMPLEMENT-REGULATORY FACTORS

Background. Clinical and experimental studies have suggested that comp lement activation may play a role in tumor cytotoxicity. Little inform ation is available concerning the presence of complement activation an d the localization of complement-regulatory factors in cells or tissue s of malignant tumors. The aim of the present study was to examine, us ing immunohistochemistry and immunoelectron microscopy, whether the co mplement system is activated in tissues of thyroid carcinoma and wheth er thyroid carcinoma cells are protected from cell lysis by in situ co mplement activation. Methods. Fresh tissues were obtained by thyroidec tomy from 15 patients with papillary carcinomas, 7 with follicular car cinomas, and 5 with follicular adenomas. In addition, five specimens o f histologically normal thyroid tissue and five specimens of chronical ly inflamed tissue adjacent to thyroid neoplasms were studied. Immunoh istochemical and immunoelectron microscopic localization of complement components, C3d and C5b-9, and the complement-regulatory factors, suc h as s-protein, decay-accelerating factor (CD55), membrane cofactor pr otein (CD46), complement receptor types 1 (CD35) and 2 (CD21), and pro tectin (CD59), were examined in these tissues. Results. The staining p atterns 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 subepith elial and vascular basement membranes and attached to the cell surface of thyroid follicular cells. Decay-accelerating factor (CD55) was pre sent 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-cel l interaction, but rarely on the luminal surface, whereas protectin wa s expressed strongly on the luminal surface and often on the basal cel l border but rarely on the lateral membrane. Neither complement recept or type 1 (CD35) nor complement receptor type 2 (CD21) was expressed o n any thyroid follicular cells. Conclusions. The present study confirm ed 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 comp lement activation in multiple phases by complete coverage of the entir e cell membrane surface with complement-regulatory factors. These find ings were similar to those found in nonneoplastic thyroid follicular c ells.