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The Dichotomy in the Preinvasive Neoplasia to Invasive Carcinoma Sequence in the Pancreas: Differential Expression of MUC1 and MUC2 Supports the Existence of Two Separate Pathways of Carcinogenesis

Open access
Adsay, N. Volkan, Merati, Kambiz, Andea, Aleodor, Sarkar, Fazlul, Hruban, Ralph H., Wilentz, Robb E., Goggins, Micheal, Iocobuzio-Donahue, Christine, Longnecker, Daniel S., Klimstra, David S.·2002·Modern Pathology

Abstract

Emerging evidence suggests a dichotomy in the dysplasia-CIS-invasive carcinoma sequence in the pancreas. Pancreatic intraepithelial neoplasms (PanINs; small, incidental duct lesions) progress to invasive ductal adenocarcinomas (5-y survival of < 15%), whereas intraductal papillary mucinous neoplasms (large, intraductal tumors with ductal dilatation) are often associated with colloid carcinoma (5-y survival of > 55%). We explored the relationship of these lesions by examining the expression of MUC1 and MUC2, glycoproteins reportedly reflecting "aggressive" and "indolent" phenotypes in pancreas cancer, respectively. Immunohistochemical labeling with MUC1 (clone Ma695) and MUC2 (clone Ccp58) antibodies was performed on PanINs (n = 43), intraductal papillary mucinous neoplasms (n = 74), ductal adenocarcinomas (n = 136), and colloid carcinomas (n = 15). Fifty-four percent of the intraductal papillary mucinous neoplasms expressed MUC2, whereas none of the PanINs did. In contrast, PanINs, especially higher grade lesions, were often positive for MUC1 (61% of PanIN 3), whereas the expression of this glycoprotein was infrequent in intraductal papillary mucinous neoplasms (20%). This dichotomy was further accentuated in the invasive carcinomas with which these two preinvasive pathways are respectively associated: all colloid carcinomas were MUC2+ (100%) and MUC1- (0%), whereas the labeling pattern was the reverse for ductal adenocarcinomas: 63% were MUC1+ and only 1% were MUC2+. These results support a dichotomy in the dysplasia-CIS sequence in the pancreas. Because these two pathways often lead to different types of invasive carcinomas, this is an invaluable model for the study of carcinogenesis. The findings here also support the previous impression that MUC2 (the mucin associated with gel formation) is a marker of the "indolent" pathway (intraductal papillary mucinous neoplasm and colloid carcinoma), whereas MUC1 (the glycoprotein known to have an inhibitory role in cell-cell and cell-stroma interactions as well as in immunoresistance of tumor cells) is a marker of the "aggressive" pathway (PanIN to ductal adenocarcinoma).

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Metadata

Authors
Adsay, N. V., Merati, K., Andea, A., Sarkar, F., Hruban, R. H., Wilentz, R. E., Goggins, M., Iocobuzio-Donahue, C., Longnecker, D. S., & Klimstra, D. S.
Venue
Modern Pathology
Published
2002-10
Volume
15
Issue
10
Pages
1087-1095
ISSN
  • 0893-3952 (ISSN-L)
  • 1530-0285
OpenAlex
W2071082888
Cited by
295
References
46
FWCI
6.44
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: The Dichotomy in the Preinvasive Neoplasia to Invasive Carcinoma Sequence in the Pancreas: Differential Expression of MUC1 and MUC2 Supports the Existence of Two Separate Pathways of Carcinogenesis. https://app.cochat.ai/papers/10.1097/01.mp.0000028647.98725.8b
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Adsay, N. V., Merati, K., Andea, A., Sarkar, F., Hruban, R. H., Wilentz, R. E., Goggins, M., Iocobuzio-Donahue, C., Longnecker, D. S., & Klimstra, D. S. (2002). The Dichotomy in the Preinvasive Neoplasia to Invasive Carcinoma Sequence in the Pancreas: Differential Expression of MUC1 and MUC2 Supports the Existence of Two Separate Pathways of Carcinogenesis. Modern Pathology. https://doi.org/10.1097/01.mp.0000028647.98725.8b

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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