Analyses of p53 antibodies in sera of patients with lung carcinoma define immunodominant regions in the p53 protein

Abstract

Summary Antibodies specific for human p53 were analysed in sera of lung cancer patients. We detected p53 antibodies in the sera of 24% (10/42) of patients with lung carcinoma. The distribution was as follows: 4/9 small-cell lung carcinomas (SCLCs), 2/18 squamous cell lung carcinomas (SCCs), 2/10 adenocarcinomas (ADCs) and 2/5 large-cell lung carcinomas (LCCs). p53 antibodies were always present at the time of diagnosis and did not appear during progression of the disease. Using an original peptide-mapping procedure, we precisely localised the p53 epitopes recognised by p53 antibodies. Immunodominant epitopes reacting with antibodies were localised in the amino and carboxy termini of the protein, similar to those found in breast carcinoma patients or in animals immunised with p53. In light of these data, we suggest that p53 antibodies occur via a self-immunisation process that is the consequence of p53 accumulation in tumour cells. p53 antibodies were also detected in two patients without detected malignant disease. One of these patients died 6 months later of lung carcinoma, suggesting that p53 antibodies may be a precocious marker of p53 alteration.

Detection of p73 antibodies in patients with various types of cancer: immunological characterization

“…These antibodies recognize immunodominant epitopes localized in the amino-and, to a lesser extent, in the carboxy-terminus of human p53 (Lubin et al, 1993;Schlichtholz et al, 1994;Vennegoor et al, 1997). Antibodies specific for the central region are always poorly abundant or absent (Lubin et al, 1993).…”

Increased serum p53 antibody levels indicate poor prognosis in patients with colorectal cancer

“…Studies have shown that 9-26% of patients with different carcinomas have mounted a humoral immune response (antibodies) to abnormal p53 protein (Caron de Fromental et al, 1987;Levine et al, 1991;Angelopoulou et al, 1994). Thus, anti-p53 antibodies may be a serological marker for malignancy.Recent studies have shown increased serum antibody levels against mutant p53 protein in patients with breast (Crawford et al, 1982;Davidoff et al, 1992;Schlichtholtz et al, 1992;Mudenda et al, 1994), lung (Winter et al, 1992;Schlichtholtz et al, 1994) and Immunohistochemical analysis of overexpression of p53 protein p53 protein overexpression was evaluated using an immunohistochemical method (Kressner et al, 1996). Briefly, DO-7 monoclonal antibody was used in combination with biotinylated horse antimouse IgG antibody as secondary antibody, followed by avidin-biotin blocking kit and ethyl carbazole substrate.…”

“…Recent studies have shown increased serum antibody levels against mutant p53 protein in patients with breast (Crawford et al, 1982;Davidoff et al, 1992;Schlichtholtz et al, 1992;Mudenda et al, 1994), lung (Winter et al, 1992;Schlichtholtz et al, 1994) and colorectal cancer (Houbiers et al, 1995;Angelopoulou et al, 1997). Two of the studies in breast cancer patients have indicated that the occurrence of p53 antibodies may be a useful determinant with regard to poor prognosis (Schlichtholtz et al, 1992;Mudenda et al, 1994).…”

Measurement and evaluation of serum anti-p53 antibody levels in patients with lung cancer at its initial presentation: a prospective study

“…In a lunc cancer series. Schlichtholz et al (1994) reported that anti-p53 antibodies were found in sera in 20.0% of patients with adenocarcinoma. [Schlichtholz et al 1994: Trivers et al 1996 as well as our own.…”

“…Schlichtholz et al (1994) reported that anti-p53 antibodies were found in sera in 20.0% of patients with adenocarcinoma. [Schlichtholz et al 1994: Trivers et al 1996 as well as our own. anti-p53 levels determined by ELISA are continuously plotted for :ancer patients and appear to be higher than those in normal control subjects.…”