PAM4 Enzyme Immunoassay Alone and in Combination With CA
19-9 for the Detection of Pancreatic Adenocarcinoma
David V. Gold, PhD1; Jochen Gaedcke, MD2; B. Michael Ghadimi, MD2; Michael Goggins, MD3; Ralph H. Hruban, MD3;
Mengling Liu, PhD4; Guy Newsome, BS1; and David M. Goldenberg, ScD, MD1
BACKGROUND: The monoclonal antibody PAM4 has high specificity for pancreatic ductal adenocarcinoma (PDAC), as well as its pre-
cursor 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 ¼
298), other cancers (N ¼ 99), benign disease of the pancreas (N ¼ 120), and healthy adults (N ¼ 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 signifi-
cance 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 sensi-
tivity 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 ¼ .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 bio-
marker serum assay for the detection of early stage PDAC. Cancer 2013;119:522-8. V
C 2012 American Cancer Society.
KEYWORDS: pancreatic cancer, pancreatitis, diagnosis, early detection, PAM4, carbohydrate antigen (CA) 19-9.
Although imaging methods play an important role in the detection of pancreatic cancer,1-4especially in selecting a course
of therapy, there are limitations with respect to the detection of small lesions,1as well as for discriminating pancreatic can-
early.7Withno effectivetreatmentforadvancedpancreaticcancer, theprognosis forthemajorityofpatientsis dismal.
Biomarkers potentially can provide a more cost-effective means for early detection and diagnosis, and a great deal of
effort has been devoted to biomarker research.8-16Such biomarkers also are in high demand for the detection and diagno-
sis of pancreatic cancer, especially early stage disease, but to the best of our knowledge no single assay to date has achieved
diagnosis, imaging, and treatment of cancer, and have focused on the assessment of the PAM4 antibody, which binds to a
large-size mucin17for the detection and diagnosis of pancreatic ductal adenocarcinoma (PDAC),18-21for imaging,22,23
that the reactivityof the PAM4antibodyis highlyrestricted to PDAC,and that the specific PAM4epitope is expressed (or
becomes accessible) at the earliest stages of PDAC development (ie, the precursor lesions pancreatic intraepithelial neopla-
sia [PanIN], intraductal papillary mucinous neoplasia, and mucinous cystic neoplasm).17,18The PAM4 antigen is absent
inar cells, nor isolated acinar-ductal metaplasia (ADM) within surgical specimens obtained from > 50 patients with
chronic pancreatitis (CP).20-22However, the PAM4 antigen was expressed by invasive PDAC identified in 2 cases, and in
PanINprecursorlesionsfound inseveralofthe specimens.
DOI: 10.1002/cncr.27762, Received: April 9, 2012; Revised: May 21, 2012; Accepted: June 12, 2012, Published online August 16, 2012 in Wiley Online Library
Corresponding author: David V. Gold, PhD, Center for Molecular Medicine and Immunology, Garden State Cancer Center, 300 The American Rd, Morris Plains,
NJ 07950; Fax: (973) 844-7020; firstname.lastname@example.org
1Center for Molecular Medicine and Immunology, Garden State Cancer Center, Morris Plains, New Jersey;
University Medical Center Gottingen, Gottingen, Germany;3The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutes, Baltimore,
Maryland;4Division of Biostatistics, New York University School of Medicine, New York, New York
2Department of General and Visceral Surgery,
February 1, 2013
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