P53 AUTOANTIBODIES IN PATIENTS WITH PANCREATITIS AND PANCREATIC-CARCINOMA

In human pancreatic carcinoma (PCa) mutations in the p53 tumor suppres sor gene are present in up to 50% of cases. Conformational change and cellular accumulation, together with subsequent release of mutant and normal p53 protein from transformed cells, may initiate a B-cell respo nse with generation of circulating autoantibodies to p53 protein (anti -p53). In the present study we analyzed the sera of 85 consecutive pat ients with acute pancreatitis (N = 19), chronic pancreatitis (N = 33), and PCa (N = 33) to evaluate the specificity of autoantibodies to p53 protein as a serological marker for PCa. Detection of anti-p53 was pe rformed using an enzyme-linked immunosorbent assay system with immobil ized recombinant wild-type p53 protein. Autoantibodies to p53 were det ectable in 1 of 19 patients with acute (5.3%) and in 4 of 33 patients with chronic pancreatitis (12.1%). All anti-p53-positive patients with acute or chronic pancreatitis were carefully examined and no underlyi ng malignant disease was found. During follow-up (range, 281-647 days; mean, 472 days) none of these patients showed any evidence for subseq uent development of PCa or any other malignant disease, in patients wi th PCa, anti-p53 was detected in 6 of 33 cases, resulting in a sensiti vity of 18.2% with a specificity of 90.4%. In contrast to anti-p53, de tection of serum carbohydrate antigen (CA 19-9) resulted in a sensitiv ity and specificity of 69.7 and 71.2% (CA 19-9, > 37 U/ml) and 51.5 an d 96.2% (CA 19-9, > 100 U/ml) for the detection of PCa, respectively. Taken together, the sensitivity of anti-p53 formation was Low in patie nts with PCa (18.2%). Furthermore, the detection of anti-p53 was not s pecific for malignancy, indicating that severe inflammatory processes may also induce anti-p53 formation.