Differentiation of pancreatic ductal adenocarcinoma from chronic pancreatitis by PAM4 immunohistochemistry.
BACKGROUND
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 early-stage 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.


METHODS
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.
From the Departments of Pathology, Microbiology, and Immunology (Dr Shi) and Surgical Oncology (Dr Merchant), Vanderbilt University Medical Center, Nashville, Tennessee; and the Center for Molecular Medicine and Immunology, Garden State Cancer Center, Morris Plains, New Jersey (Mr Newsome and Drs Goldenberg and Gold).
Chanjuan
C
Shi
Nipun
N
Merchant
Guy
G
Newsome
David M
DM
Goldenberg
David V
DV
Gold
D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry; D018396:Mucin-1 / Q000378:metabolism*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010179:Pancreas / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D010180:Pancreatectomy; D010181:Pancreatic Cyst / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D010183:Pancreatic Ducts / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D050500:Pancreatitis, Chronic / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D011230:Precancerous Conditions / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D046888:Tissue Array Analysis
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C060192:MUC1 protein, human; D018396:Mucin-1; C550275:PAM4 protein, human