Differentiation of pancreatic ductal adenocarcinoma from chronic pancreatitis by PAM4 immunohistochemistry

Chanjuan Shi, Nipun Merchant, Guy Newsome, David M. Goldenberg, David V. Gold

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Context.-PAM4 is a monoclonal antibody that shows high specificity for pancreatic ductal adenocarcinoma (PDAC) and its neoplastic precursor lesions. A PAM4- based serum immunoassay is able to detect 71% of earlystage patients and 91% with advanced disease. However, approximately 20% of patients diagnosed with chronic pancreatitis (CP) are also positive for circulating PAM4 antigen. The specificity of the PAM4 antibody is critical to the interpretation of the serum-based and immunohistochemical assays for detection of PDAC. Objective.-To determine whether PAM4 can differentiate PDAC from nonneoplastic lesions of the pancreas. Design.-Tissue microarrays of PDAC (N = 43) and surgical specimens from CP (N = 32) and benign cystic lesions (N=19) were evaluated for expression of the PAM4 biomarker, MUC1, MUC4, CEACAM5/6, and CA19-9. Results.-PAM4 and monoclonal antibodies (MAbs) to MUC1, MUC4, CEACAM5/6, and CA19-9 were each reactive with the majority of PDAC cases; however, PAM4 was the only monoclonal antibody not to react with adjacent, nonneoplastic parenchyma. Although PAM4 labeled 19% (6 of 32) of CP specimens, reactivity was restricted to pancreatic intraepithelial neoplasia associated with CP; inflamed tissues were negative in all cases. In contrast, MUC1, MUC4, CEACAM5/6, and CA19-9 were detected in 90%, 78%, 97%, and 100% of CP, respectively, with reactivity also present in nonneoplastic inflamed tissue. Conclusions.-PAM4 was the only monoclonal antibody able to differentiate PDAC (and pancreatic intraepithelial neoplasia precursor lesions) from benign, nonneoplastic tissues of the pancreas. These results suggest the use of PAM4 for evaluation of tissue specimens, and support its role as an immunoassay for detection of PDAC.

Original languageEnglish (US)
Pages (from-to)220-228
Number of pages9
JournalArchives of Pathology and Laboratory Medicine
Volume138
Issue number2
DOIs
StatePublished - Feb 2014
Externally publishedYes

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Chronic Pancreatitis
Adenocarcinoma
Immunohistochemistry
Monoclonal Antibodies
Immunoassay
Pancreas
Serum
Neoplasms
Biomarkers
Antigens

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology

Cite this

Differentiation of pancreatic ductal adenocarcinoma from chronic pancreatitis by PAM4 immunohistochemistry. / Shi, Chanjuan; Merchant, Nipun; Newsome, Guy; Goldenberg, David M.; Gold, David V.

In: Archives of Pathology and Laboratory Medicine, Vol. 138, No. 2, 02.2014, p. 220-228.

Research output: Contribution to journalArticle

Shi, Chanjuan ; Merchant, Nipun ; Newsome, Guy ; Goldenberg, David M. ; Gold, David V. / Differentiation of pancreatic ductal adenocarcinoma from chronic pancreatitis by PAM4 immunohistochemistry. In: Archives of Pathology and Laboratory Medicine. 2014 ; Vol. 138, No. 2. pp. 220-228.
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abstract = "Context.-PAM4 is a monoclonal antibody that shows high specificity for pancreatic ductal adenocarcinoma (PDAC) and its neoplastic precursor lesions. A PAM4- based serum immunoassay is able to detect 71{\%} of earlystage patients and 91{\%} with advanced disease. However, approximately 20{\%} of patients diagnosed with chronic pancreatitis (CP) are also positive for circulating PAM4 antigen. The specificity of the PAM4 antibody is critical to the interpretation of the serum-based and immunohistochemical assays for detection of PDAC. Objective.-To determine whether PAM4 can differentiate PDAC from nonneoplastic lesions of the pancreas. Design.-Tissue microarrays of PDAC (N = 43) and surgical specimens from CP (N = 32) and benign cystic lesions (N=19) were evaluated for expression of the PAM4 biomarker, MUC1, MUC4, CEACAM5/6, and CA19-9. Results.-PAM4 and monoclonal antibodies (MAbs) to MUC1, MUC4, CEACAM5/6, and CA19-9 were each reactive with the majority of PDAC cases; however, PAM4 was the only monoclonal antibody not to react with adjacent, nonneoplastic parenchyma. Although PAM4 labeled 19{\%} (6 of 32) of CP specimens, reactivity was restricted to pancreatic intraepithelial neoplasia associated with CP; inflamed tissues were negative in all cases. In contrast, MUC1, MUC4, CEACAM5/6, and CA19-9 were detected in 90{\%}, 78{\%}, 97{\%}, and 100{\%} of CP, respectively, with reactivity also present in nonneoplastic inflamed tissue. Conclusions.-PAM4 was the only monoclonal antibody able to differentiate PDAC (and pancreatic intraepithelial neoplasia precursor lesions) from benign, nonneoplastic tissues of the pancreas. These results suggest the use of PAM4 for evaluation of tissue specimens, and support its role as an immunoassay for detection of PDAC.",
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