Overexpression of p53 protein during pancreatitis

Abstract

Summary Overexpression of p53 correlates with neoplasia in many cytological specimens. To test the specificity of overexpressed p53 as a tumour marker for the detection of pancreatic cancer, we analysed cytological specimens of pancreatic juice samples from patients with pancreatitis or pancreatic carcinoma (n = 42) for p53 protein overexpression. p53 protein overexpression was found in 59% of patients with pancreatitis and 67% of patients with pancreatic carcinoma. Thus, Kalthoff et al, 1993), and more than 50% of pancreatic carcinomas express an altered p53 tumour-suppressor gene (Barton et al, 1991;Kalthoff et al, 1993). Deletions of cyclin kinase inhibitors pl6/MTS1 (Caldas et al, 1994) and pl5/MTS2 (Naumann et al, 1996) have been described, and a new tumour-suppressor gene, DPC4, has been found very recently (Hahn et al, 1996). In spite of this progress at the molecular level, the clinical outcome of patients with pancreatic cancer is still very poor. Thus, detection of early stages of pancreatic cancer is still crucial for a better prognosis.For many cytological specimens, the detection of p53 overexpression by immunocytochemistry strongly correlates with neoplasia (Dowell et al, 1994). Our aim was to establish whether the detection of p53 overexpression in cytological specimens from pancreatic juice samples, collected during ERCP (endoscopic retrograde cholangiopancreaticography), may be useful in detecting early stages of pancreatic carcinoma.p53 protein overexpression was detected in nearly 60% of cytological specimens from patients with pancreatitis but without any sign of pancreatic cancer for up to 5 years (median follow-up) after ERCP. This indicates that, in the case of pancreatic disease, p53 protein overexpression does not correlate with neoplasia. However p53 seems to play an important role during pancreatitis, as apoptotic cell death has been observed during chronic disease. This is in line with the function of p53 as an inductor of apoptotic cell death (Lane, 1992 MATERIALS AND METHODS Preparation of cytological specimens by cytospin of pancreatic juicePancreatic juice samples were collected during diagnostic ERCP from a total of 42 patients. One group comprised 27 patients suffering from chronic pancreatitis. The other group had 15 patients with pancreatic ductal adenocarcinomas, the vast majority of which were in stage II and III. Sample preparation was performed exactly as described previously (Schmiegel et al, 1990). Median follow-up was 5 years in the group of pancreatitis patients. During this period, no pancreatic cancer cases were observed. Antibodies and immunoperoxidase studiesThe p53-specific monoclonal antibodies PAbl801, PAb240 and PAbl620 were obtained from Oncogene Sciences (Dianova, Hamburg). The polyclonal antiserum against recombinant human p53 (CM-1) was purchased from Medac (Hamburg). Immunoperoxidase studies were performed exactly as described previously (Kalthoff et al, 1993). Samples were scored positive when at least 5% of the cells from the investigated cytospin were...

Molecular Diagnosis of Early Pancreatic Ductal Adenocarcinoma in High-Risk Patients

“…Immunocytology with p53 antibodies using cells from pancreatic duct brushings was shown by Iwao et al [169,181] to detect 36 out of 44 (82%) pancreatic carcinomas. Unfortunately, a similar analysis by Maacke et al [168] that confirmed this finding, in that 10 of 15 (67%) patients with pancreatic carcinoma had p53 over-expression in pancreatic cells obtained endoscopically, also found p53 over-expression in 16 of 27 (59%) patients with chronic pancreatitis. It is likely that p53 over-expression in the ductular cells of chronic pancreatitis represents increased p53 activity rather than a manifestation of TP53 mutations.…”

Autoimmunity to the p53 Protein is a Feature of Systemic Lupus Erythematosus (SLE) Related to Anti-DNA Antibodies

“…This, of course, could occur through an idiotypic network triggered by p53 autoimmunity [19,20]. The induction of the anti-p53 antibodies can be accounted for by the accumulation of the p53 molecule, not only in tumour cells [21], but also in activated inflammatory cells [22]. The accumulation of p53 apparently can trigger an autoimmune response to the molecule [23,24].…”

Staining for p53 and Ki-67 increases the sensitivity of EUS-FNA to detect pancreatic malignancy

“…First, in contrast to this study, false positive p53 stainings in be nign pancreatic lesions were demonstrated in previous studies at rates ranging from 3% to about 10% [12,13,26,27,[31][32][33] . Indeed, wild-type p53 over-expression can be inducible under certain benign conditions, such as during inflammation in response to TNF-alpha [34] . Second, this study showed a lower rate of p53 IH positivity in malignant cases: 29% versus the usual range of 50% to 70% in other EUS-FNA and biopsy series [13,14,32] .…”