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

ArticleinCancer 119(3) · February 2013with6 Reads
DOI: 10.1002/cncr.27762 · Source: PubMed
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.
    • "Moreover, with regard to PDAC diagnosis, the biomarker should be able to distinguish affected patients from those with other pancreatic diseases, and this be tested successfully in a different study sample. Non-invasive laboratory tests that are currently used such as CA 19–9, those for liver function, and PAM4 monoclonal antibody are non-specific as they can also be expressed in other pancreatic diseases [89][90][91]. This poses challenges for accurate PDAC diagnosis because the majority of patients who get a confirmed diagnosis of PDAC by imaging and pathological examination initially present with moderate to severe pan- creatitis [92]. "
    [Show abstract] [Hide abstract] ABSTRACT: Objectives: A systematic review of the role of cytokines in clinical medicine as diagnostic, prognostic, or predictive biomarkers in pancreatic ductal adenocarcinoma was undertaken. Materials and methods: A systematic review was conducted according to the 2009 PRISMA guidelines. PubMed database was searched for all original articles on the topic of interest published until June 2015, and this was supplemented with references cited in relevant articles. Studies were evaluated for risk of bias using the Quality in Prognosis Studies tools. Results: Forty one cytokines were investigated with relation to pancreatic ductal adenocarcinoma (PDAC) in 65 studies, ten of which were analyzed by more than three studies. Six cytokines (interleukin[IL]-1β, -6, -8, -10, vascular endothelial growth factor, and transforming growth factor) were consistently reported to be increased in PDAC by more than four studies; irrespective of sample type; method of measurement; or statistical analysis model used. When evaluated as part of distinct panels that included CA19-9, IL-1β, -6 and -8 improved the performance of CA19-9 alone in differentiating PDAC from healthy controls. For example, a panel comprising IL-1β, IL-8, and CA 19-9 had a sensitivity of 94.1% vs 85.9%, specificity of 100% vs 96.3%, and area under the curve of 0.984 vs 0.925. The above-mentioned cytokines were associated with the severity of PDAC. IL-2, -6, -10, VEGF, and TGF levels were reported to be altered after patients received therapy or surgery. However, studies did not show any evidence of their ability to predict treatment response. Conclusion: Our review demonstrates that there is insufficient evidence to support the role of individual cytokines as diagnostic, predictive or prognostic biomarkers for PDAC. However, emerging evidence indicates that a panel of cytokines may be a better tool for discriminating PDAC from other non-malignant pancreatic diseases or healthy individuals.
    Full-text · Article · May 2016
    • "The PAM4 marker, an antigen produced by tumor cells, shows a sensitivity of 76% with a specificity of 96% in the diagnosis of pancreatic adenocarcinoma, including in the early stages of onset. The association of CA 19–9 concentrations to PAM4 conferred 84% specificity in diagnosis , regardless of serum bilirubin concentrations [20]. One scenario in which CA 19–9 results must be interpreted with caution is in jaundiced patients. "
    [Show abstract] [Hide abstract] ABSTRACT: The diagnosis of pancreatic cystic neoplasms has become more accurate recently. In some cases, however, doubt remains regarding the lesion's malignant potential. CA 19-9 has long been identified as a reliable biomarker in differentiating pancreatic benign and malignant lesions, especially in non-jaundiced patients. We report a case of a young female who presented with a mucinous lesion in the tail of the pancreas and a serum CA 19-9 over 1,000,000 U/mL. She was taken to surgery and had a distal pancreatectomy and splenectomy. Pathology reports showed only a mucinous cystadenoma. After 1 year of follow-up, her serum CA 19-9 was normal. Following that, the work-up in these lesions, the role of the biomarker in pancreatic adenocarcinoma and in the differentiation between benign and malignant lesions is discussed.
    Full-text · Article · Dec 2015
    • "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. "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Apr 2014
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