Autoimmune response to anti-apoptotic protein survivin and its association with antibodies to p53 and c-myc in cancer detection

Abstract

Survivin, an inhibitor of apoptotic protein, is over-expressed in many cancers but not in normal differentiated adult tissues. Recently, antibodies to survivin have been demonstrated in patients with lung and colorectal cancer. Whether antibodies to survivin can be used as a marker for the diagnosis of cancer, and how antibody to survivin is related to antibodies against tumor suppressor protein p53 and oncoprotein c-myc remains to be evaluated. In the present study, the full-length recombinant proteins survivin, p53 and c-myc, were expressed and used as antigens in enzyme-linked immunosorbent assay (ELISA) and Western blot for the detection of antibodies to these three proteins. Sera from 1137 patients with 11 different types of cancer were analyzed. Antibodies to survivin were detected in 8.4% (96/1137), with a significant difference from the control groups consisting of normal individuals and autoimmune disease patients (p < 0.05). Of 1137 cancer sera, 546 were also tested for the presence of antibodies to p53 and c-myc. Frequencies of antibodies to p53 and c-myc were 11.5 and 12.3%, respectively. Although antibodies to either one of three antigens do not reach levels of sensitivity, which could become routinely useful in diagnosis, it appears that there are different patterns of antibody frequency in individual cancer type. The results also indicated that when the presence of antibody to any one of these three antigens was considered, the cumulative frequency was increased to 27.3% (149/546) for the total group of cancer patients. It became apparent from our data that the combination of antibodies might acquire higher sensitivity. (c) 2005 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved.