Aberrant expression of MUC3 and MUC4 membrane-associated mucins and sialyl Le(x) antigen in pancreatic intraepithelial neoplasia.
BACKGROUND
Ductal adenocarcinoma of the pancreas has recently been suggested to arise from histologically identifiable ductal lesions known as pancreatic intraepithelial neoplasia (PanINs). Altered levels and patterns of mucin gene expression have been reported to occur in epithelial cancers.


OBJECTIVE
To examine the pattern of expression of membrane-associated mucins, MUC3 and MUC4, and a mucin-associated carbohydrate tumor antigen, sialyl Le(x), in these precursor lesions and ductal adenocarcinoma of the pancreas.


METHODS
A total of 144 PanIN lesions and 85 cases of ductal adenocarcinoma of the pancreas were examined by using immunohistochemistry and in situ hybridization methods.


RESULTS
MUC3 showed a progressive increase in expression in PanINs of increasing dysplasia and was also highly expressed in ductal adenocarcinoma. In contrast, neoexpression of MUC4 and sialyl Le(x) antigen was observed, mainly in PanIN-3 and ductal adenocarcinoma. In addition, a decrease in the expression of MUC3 and MUC4 was correlated with the degree of de-differentiation of the tumor.


CONCLUSIONS
Aberrant expression of membrane mucins MUC3 and MUC4 and of a mucin-associated carbohydrate tumor antigen Sialyl Le(x) in PanINs and adenocarcinoma further supports the progression model for pancreatic adenocarcinoma.
Park
Hee-Ug
HU
Gastrointestinal Research Laboratory, Veterans Affairs Medical Center, San Francisco, California 94121, USA.
Kim
Jong-Woo
JW
Kim
Grace E
GE
Bae
Han-Ik
HI
Crawley
Suzanne C
SC
Yang
Stacey C
SC
Gum
James R
JR
Batra
Surinder K
SK
Rousseau
Karine
K
Swallow
Dallas M
DM
Sleisenger
Marvin H
MH
Kim
Young S
YS
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D018450:Disease Progression; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D055263:Mucin-3; D055264:Mucin-4; D009077:Mucins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009844:Oligosaccharides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen
C524658:MUC4 protein, human; D055263:Mucin-3; D055264:Mucin-4; D009077:Mucins; D009844:Oligosaccharides; D012333:RNA, Messenger; D000080506:Sialyl Lewis X Antigen