Detection of Early-Stage Pancreatic Adenocarcinoma

作者:Gold David V*; Goggins Michael; Modrak David E; Newsome Guy; Liu Mengling; Shi Chanjuan; Hruban Ralph H; Goldenberg David M
来源:Cancer Epidemiology Biomarkers & Prevention, 2010, 19(11): 2786-2794.
DOI:10.1158/1055-9965.EPI-10-0667

摘要

Background: Pancreatic adenocarcinoma is an almost universally lethal disease, in large part, due to our inability to detect early-stage disease. Monoclonal antibody PAM4 is reactive with a unique biomarker expressed by > 85% of pancreatic adenocarcinomas. In this report, we examined the ability of a PAM4-based immunoassay to detect early-stage disease. Materials and Methods: The PAM4-based immunoassay was used to quantitate antigen in the serum of healthy volunteers (n = 19), patients with known pancreatic adenocarcinoma (n = 68), and patients with a primary diagnosis of chronic pancreatitis (n = 29). Results: Sensitivity for detection of pancreatic adenocarcinoma was 82%, with a false-positive rate of 5% for healthy controls. Patients with advanced disease had significantly higher antigen levels than those with early-stage disease (P < 0.01), with a diagnostic sensitivity of 91%, 86%, and 62% for stage 3/stage 4 advanced disease, stage 2, and stage 1, respectively. We also evaluated chronic pancreatitis sera, finding 38% positive for antigen; however, this was discordant with immunohistochemical findings that suggest the PAM4 antigen is not produced by inflamed pancreatic tissue. Furthermore, several of the serum-positive pancreatitis patients, for whom tissue specimens were available for pathologic interpretation, had evidence of neoplastic precursor lesions. Conclusions: These results suggest the use of the PAM4 serum assay to detect early-stage pancreatic adenocarcinoma and that positive levels of PAM4 antigen are not derived from inflamed pancreatic tissues but rather may provide evidence of subclinical pancreatic neoplasia. Effect: The ability to detect pancreatic adenocarcinoma at an early stage could provide for early therapeutic intervention with potentially improved patient outcomes. Cancer Epidemiol Biomarkers Prev; 19(11); 2786-94.

  • 出版日期2010-11