Immunohistochemical study of claudin 18 involvement in intestinal differentiation during the progression of intraductal papillary mucinous neoplasm.
OBJECTIVE
A comparison was made between pancreatic ductal adenocarcinoma (PDAC), pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous carcinoma (IPMC) in order to understand the association between several markers and malignant potential.


METHODS
Fifteen surgically resected PDACs and four IPMCs were subjected to immunohistochemistry with primary antibodies to Ki-67, p53, MUC2, Gli-1, and Claudin-18 (CLDN18).


RESULTS
Ki-67, P53, MUC2, Gli-1 and CLDN18 were positive in 6 (50%), 10 (66.6%), 0 (0%), 4 (26.6%), and 6 (40%) of the 15 PDACs, respectively. Low- to high-grade PanIN complexes were found in 2 out of the 15 PDACs. Gli-1 was continuously expressed in low- and high-grade PanINs. CLDN18 was specifically expressed in high-grade PanINs, whereas the corresponding invasive tubules did not express CLDN18. P53 was positively stained in one of the 4 IPMCs in which minimally invasive tubular type carcinomas were observed. Ki-67 and CLDN18 were positively stained in all 4 IPMCs. CLDN18 was specifically expressed in intestinal-type components of IPMCs.


CONCLUSIONS
CLDN18 is involved in intestinal-type epithelial differentiation in the progression of IPMCs, contradicting the previous knowledge of its specificity in gastric epithelial differentiation.
Sanada
Yuichi
Y
Department of Surgical Oncology, Gifu graduate School of Medicine, 1-1, Yanagido, Gifu City, 501-1194, Gifu, Japan. ysanadasurg@hotmail.com
Hirose
Yoshinobu
Y
Osada
Shinji
S
Tanaka
Yoshihiro
Y
Takahashi
Takao
T
Yamaguchi
Kazuya
K
Yoshida
Kazuhiro
K
D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000473:pathology; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D057167:Claudins; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D007422:Intestines / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies
C486683:CLDN18 protein, human; D057167:Claudins; D008565:Membrane Proteins