Serum anti-p53 autoantibodies from patients with idiopathic pulmonary fibrosis associated with lung cancer

Abstract

Mutations of the tumour suppressor gene p53 lead to accumulation of the mutated p53 protein and subsequent production of antoantibodies against p53 proteins, which are also detected in lung cancer. Lung cancer is frequently associated with idiopathic pulmonary fibrosis (IPF). Therefore, we hypothesized that there might be a relationship between the p53 mutation and high prevalence of lung cancer in IPF. To test this hypothesis, we measured serum p53 antibody levels by an ELISA in various lung diseases including lung cancer (n=98), IPF (n=46; with lung cancer, n=14 and without lung cancer, n=32), pulmonary emphysema (PE, n=23) and healthy controls (HC, n=93). The median values of the serum anti-p53 antibody in each group were 8.78, 9.18, 8.08 and 4.95 for patients with lung cancer, IPF with lung cancer, IPF without lung cancer and PE, respectively, and 2.2 for the healthy control group. The groups of IPF (with and without lung cancer) showed a similar level of median values to the lung cancer group and a tendency for a higher level than the PE group. When the cut-off value was set at 7.7 according to the 95% specificity level for normal control, the incidence of positive anti-p53 antibody was significantly higher in lung cancer (61.2%), IPF with lung cancer (57.1%) and IPF without lung cancer (53.1%) than PE (21.7%). These results suggest that p53 mutations occur frequently and substantially in IPF, resulting in a high prevalence of lung cancer.