HUMAN CARCINOMAS VARIABLY EXPRESS THE COMPLEMENT INHIBITORY PROTEINS CD46 (MEMBRANE COFACTOR PROTEIN), CD55 (DECAY-ACCELERATING FACTOR), AND CD59 (PROTECTIN)

Normal human tissues express membrane-associated complement inhibitory proteins that protect these tissues from damage by autologous complem ent. To determine whether neoplasms also express these proteins, we ex amined the distribution of the complement inhibitors decay-acceleratin g factor (DAF), CD59 (protectin), and membrane cofactor protein in fro zen samples of human breast, colon, kidney, and lung carcinomas and in adjacent non-neoplastic tissues, using immunohistochemistry. All samp les were also studied for deposition of C3 fragments and activated C5b -9. Differences between normal tissues and the corresponding neoplasms were often observed, with loss or gain of expression of one or more i nhibitors. Ductal carcinomas of the breast showed the most variation i n phenotype: some tumors expressed different combinations of two or th ree inhibitors. Colon carcinomas, by contrast, stained intensely for a ll inhibitors. Renal cell carcinomas had weak to moderate expression o f one to three inhibitors, generally DAF and CD59, whereas non-small c ell carcinomas of the lung usually expressed CD59 and membrane cofacto r protein with variable DAF immunoreactivity. The two small cell carci nomas of the lung showed little or no staining for any inhibitor. Acti vated C5b-9 deposition was seen adjacent to tumor nests in a minority of carcinomas and showed no correlation with complement inhibitor expr ession. C3 fragment deposition was minimal. Our results demonstrate th at most carcinomas, with the exception of small cell carcinomas of the lung, do express one or more complement inhibitors at a level likely to inhibit complement-mediated cellular damage. Unexpectedly, large qu antities of DAF and CD59 were often observed in tumor stroma, with onl y limited deposition in normal connective tissue. This suggests that c arcinomas may supplement the activity of membrane-associated complemen t inhibitors by release of soluble forms of DAF and CD59 into the surr ounding extracellular matrix.