Proteomic Mapping of p53 Immunogenicity in Pancreatic, Ovarian, and Breast Cancers

abstract

 ep·i·tope

(ĕp′ĭ-tōp′)n. A localized region on the surface of an antigen capable of eliciting an immune response and of combining with a specific antibody to counter that response.

Purpose

Mutations in TP53 induce autoantibody immune responses in a subset of cancer patients, which have been proposed as biomarkers for early detection. Here, we investigate the association of p53 specific autoantibodies with multiple tumor subtypes and determine the association with p53 mutation status and epitope specificity.

Experimental Design

IgG p53 autoantibodies (p53-AAb), were quantified in 412 serum samples using a programmable ELISA assay from patients with serous ovarian, pancreatic adenocarcinoma, and breast cancer. To determine if patients generated mutation specific autoantibodies we designed a panel of the most relevant 51 p53 point mutant proteins....

Results

We detected p53-AAb with sensitivities of 58.8% (ovarian), 22% (pancreatic), 32% (triple negative breast cancer), and 10.2% (HER2+ breast cancer) at 94% specificity. Sera with p53-AAb contained broadly-reactive autoantibodies to 51 displayed p53 mutant proteins, demonstrating a polyclonal response to common epitopes. All p53-AAb displayed broad polyclonal immune response to both continuous and discontinuous epitopes at the N- and C-terminus as well as the DNA binding domain.

Conclusion and clinical relevance

In this comprehensive analysis, mutations in tumor p53 induce strong, polyclonal autoantibodies with broadly reactive epitope specificity.