PAM4 enzyme immunoassay alone and in combination with CA 19-9 for the detection of pancreatic adenocarcinoma

Abstract

Background: The monoclonal antibody PAM4 has high specificity for pancreatic ductal adenocarcinoma (PDAC), as well as its precursor lesions, but has not been found to be reactive with normal and benign pancreatic tissues. The objective of the current study was to evaluate a PAM4-based serum enzyme immunoassay alone and in combination with the carbohydrate antigen (CA) 19-9 assay for the detection of PDAC, with particular attention to early stage disease.

Methods: Sera from patients with confirmed PDAC (N = 298), other cancers (N = 99), benign disease of the pancreas (N = 120), and healthy adults (N = 79) were evaluated by a specific enzyme immunoassay for the concentration of PAM4 and CA 19-9 antigen levels by blinded analyses. All tests for statistical significance were 2-sided.

Results: The overall sensitivity for PAM4 detection of PDAC was 76%, with 64% of patients with stage I disease also identified. The detection rate was considerably higher (85%) for patients with advanced disease. The assay demonstrated high specificity compared with benign pancreatic disease (85%), with a positive likelihood ratio of 4.93. CA 19-9 provided an overall sensitivity of 77%, and was positive in 58% of patients with stage I disease; however, the specificity was significantly lower for CA 19-9 (68%), with a positive likelihood ratio of 2.85 (P = .026 compared with PAM4). It is important to note that a combined PAM4 and CA 19-9 biomarker serum assay demonstrated an improved sensitivity (84%) for the overall detection of PDAC without a significant loss of specificity (82%) compared with either arm alone.

Conclusions: The PAM4 enzyme immunoassay identified approximately two-thirds of patients with stage I PDAC with high discriminatory power with respect to benign, nonneoplastic pancreatic disease. These results provide a rationale for testing patient groups considered to be at high risk for PDAC with a combined PAM4 and CA 19-9 biomarker serum assay for the detection of early stage PDAC.

Conflict of interest statement

Conflict of interest disclosures: David M. Goldenberg has a financial interest in Immunomedics, Inc. David M Goldenberg and David V Gold are patent inventors. The other authors disclose no conflicts of interest.

Copyright © 2012 American Cancer Society.

Figures

Figure 1

Accuracy for quantitation of PAM4-antigen spiked into normal human serum. A consistent linear relationship was observed for nominal versus measured at antigen concentrations at or near the cutoff value of 2.4 units/mL.

Figure 2

ROC curves for the performance of the PAM4-based immunoassay; pancreatic ductal adenocarcinoma vs chronic pancreatitis on the left, and pancreatic ductal adenocarcinoma vs all patients with diagnoses of benign pancreatic disease (including chronic pancreatitis) on the right. Values for the area under the curves (AUC) and 95% confidence limits are provided.

Figure 3

ROC curves for the performance of the PAM4-immunoassay (—— bold black), CA19-9-immunoassay (– – – dashed black), and the combined-biomarker assay ( dotted gray). On the left are the ROC curves for discrimination of pancreatic ductal adenocarcinoma vs chronic pancreatitis, and on the right, ROC curves for discrimination of pancreatic ductal adenocarcinoma vs all patients with diagnoses of benign pancreatic disease (including chronic pancreatitis). Descriptive statistical values are provided in Table 3. For each of the comparisons evaluated, the combined-biomarker assay had significantly greater sensitivity for detection of pancreatic cancer when compared to either the PAM4 or CA19-9 immunoassays alone (P<0.0257 or better).