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.