Clinical significance of serum p53 antigen in patients with pancreatic carcinomas

Abstract

Background - Alterations in the p53 gene are often found in pancreatic cancers and accumulation of the p53 protein has been noted in tumour cells. Aims - To investigate whether serum p53 protein concentrations could be used as markers for p53 gene mutations in neoplasms of the pancreas. Methods - Serum p53 protein concentrations were determined by an enzyme linked immunosorbent assay (ELISA) in 104 cases of pancreatic adenocarcinoma, and 61 matched formalin fixed tissue sections were also stained by an anti-p53 DO-7 monoclonal antibody. Results - The mean serum concentration of p53 protein in the adenocarcinoma patients was 0.27 (SEM 02.02) ng/ml, and was significantly higher than in 35 healthy blood donors (0.15 (0.02) ng/ml, SD=0.11) or in 15 cases of chronic pancreatitis (0.15 (0.02) ng/ml). Adopting an arbitrary cut off value for the serum p53 protein concentration of 0.37 ng/ml, which corresponded to a value 2 SD above the mean value from the healthy blood donors, positive serum p53 protein concentrations were found in 23 out of 104 (22.1%) patients with adenocarcinomas examined, 16 out of 47 (34.0%) patients with carcinomas with distant metastases, but only seven of 57 patients (12.3%) with carcinomas without metastases (p<0.05). In 11 patients with pancreatic adenocarcinomas, the mean serum p53 protein concentration after tumour resection was 0.21 (0.05) ng/ml, and had decreased compared with the preoperative concentrations (0.25 (0.05) ng/ml) (p<0.05). There were no significant associations between the serum concentrations of p53 protein and serum concentrations of markers such as CA19-9 or CEA; however, serum concentrations of p53 protein demonstrated a potential role as an additional tumour marker. Immunohistochemical studies disclosed that the p53 protein was expressed in 28 out of 61 pancreatic adenocarcinomas (45.9%). Serum p53 protein concentrations in the positively immunostained cases were significantly higher than in the negatively immunostained cases (0.35 (0.05) ng/ml v 0.15 (0.01) ng/ml; p<0.005). Furthermore, positive immunostaining for p53 protein was found in eight out of 10 (80%) serum positive p53 protein cases with adenocarcinomas. Conclusion - An increase in serum p53 protein concentrations appears during the progression of pancreatic adenocarcinoma and correlates with the accumulation of p53 protein as a result of a mutation of the p53 gene. An analysis of p53 antigen concentrations can detect p53 gene alterations, which could be useful for the selection of treatment regimens.