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

Center for Molecular Medicine and Immunology, Garden State Cancer Center, Morris Plains, New Jersey. .
Cancer (Impact Factor: 4.89). 02/2013; 119(3). DOI: 10.1002/cncr.27762
Source: PubMed


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.

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.

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.

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.

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    • "A direct pairwise comparison of PAM4 and CA19- 9 immunoassays for discrimination of pancreatic cancer and pancreatitis resulted in a significant difference, with the PAM4 immunoassay demonstrating superior sensitivity and specificity. Approximately seven years later, Gold tested the PAM4 in a large study group of 298 pancreatic ductal adenocarcinomas (PDAC), 99 other cancers, 120 benign pancreases, and 79 healthy controls reaching 76% sensitivity and 96% specificity [22]. The study was performed blindedly. "
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    ABSTRACT: PAM4, a new monoclonal antibody (MAb) known as clivatuzumab, is highly reactive with pancreatic cancer and precursor lesions. It is absent from the normal tissues and has limited reactivity with nonpancreatic cancer. The detailed characteristic of the PAM4 epitope is unknown but recent studies have shown that it is dependent on MUC1 glycosylation status. The limited PAM4 expression pattern makes it an attractive candidate for management of pancreatic adenocarcinoma. In addition, PAM4 is a serum biomarker for diagnosis of pancreatic cancer. Several different radiolabeled immunodiagnostic and immunotherapeutic agents of PAM4 have been developed and some are being evaluated in preclinical and/or clinical studies. The review will focus on PAM4 and its potential utility for the diagnosis, radioimmunodetection, and radioimmunotherapy of pancreatic cancer.
    Journal of Immunology Research 04/2014; 2014(2):268479. DOI:10.1155/2014/268479 · 2.93 Impact Factor
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    • "PAM4 identifies a biomarker that, if present, provides a high diagnostic likelihood of the presence of pancreatic neoplasia [16-18]. Thus, clinical applications for detection of early-stage disease [16,18], and antibody-targeted imaging and therapy, are being pursued [19,20]. In addition to PDAC, the PAM4-biomarker is expressed in the precursor lesions, pancreatic intraepithelial neoplasia (PanIN, including the earliest developing lesion, PanIN-1A), and intraductal papillary mucinous neoplasia (IPMN), suggesting that there may be oncogenic significance to its expression [15]. "
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