PAM4-reactive MUC1 is a biomarker for early pancreatic adenocarcinoma.
OBJECTIVE
The anti-MUC1 monoclonal antibody (MAb), PAM4, has a high specificity for pancreatic adenocarcinoma compared with other cancers, normal tissues, or pancreatitis. In order to assess its role in early pancreatic cancer development, we examined the expression of the PAM4-reactive MUC1 in the noninvasive precursor lesions, pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasia (IPMN).


METHODS
Tissue microarrays prepared from formalin-fixed, paraffin-embedded specimens were assessed by immunohistology for expression of the PAM4-reactive, non-variable number of tandem repeats (VNTR), MUC1 epitope, and the VNTR epitope bound by the MA5 MAb.


RESULTS
The PAM4-reactive MUC1 epitope was not detected in normal pancreas but was expressed in 87% (48 of 55) of invasive pancreatic adenocarcinomas, including early stage 1 disease: PAM4 labeled 94% (44 of 47) of the earliest PanIN lesions, PanIN-1A and 1B, along with 91% (10 of 11) of PanIN-2, 40% (2 of 5) of PanIN-3, and 86% (31 of 36) of intraductal papillary mucinous neoplasia lesions. A mostly diffuse pattern of labeling was observed. A second, unrelated, anti-MUC1 MAb, MA5, showed considerably less sensitivity with early PanIN-1 lesions; only 61% (25 of 41) were positive and the labeling did not differentiate normal pancreas from PanINs.


CONCLUSIONS
The results suggest that expression of the PAM4-reactive antigen may represent an early event in the development of invasive pancreatic adenocarcinoma, and is unrelated to the VNTR peptide core epitopes of MUC1. Detection of this biomarker using immunohistology, in vitro immunoassays, and in vivo antibody-based imaging may provide new opportunities for the early detection and improved diagnosis of pancreatic cancer.
Gold
David V
DV
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ 07109, USA. dvgold@gscancer.org
Karanjawala
Zarir
Z
Modrak
David E
DE
Goldenberg
David M
DM
Hruban
Ralph H
RH
D000911:Antibodies, Monoclonal / Q000276:immunology; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000175:diagnosis* / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D018598:Minisatellite Repeats; D018396:Mucin-1 / Q000276:immunology / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D012372:ROC Curve; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D000939:Epitopes; D018396:Mucin-1