title: Aberrant expression of CDX2 is closely related to the intestinal metaplasia and MUC2 expression in intraductal papillary neoplasm of the liver in hepatolithiasis.
abstract: Intraductal papillary neoplasia of the liver (IPNL) frequently presents gastrointestinal metaplasia with aberrant expression of MUC2 and MUC5AC and oversecretion of mucin into the ductal lumen. In this study, the involvement of CDX2, a homeodomain protein involved in the regulation of intestinal development and differentiation, in the expression of MUC2 was examined in mucinous intrahepatic cholangiocarcinoma (ICC) (n=7) and IPNL with hepatolithiasis (n=19) with comparison to conventional ICC (n=11), and intraductal papillary mucinous tumor and invasive ductal carcinoma of the pancreas (n=9 and 11, respectively). A total of 33 cases of hepatolithiasis, extrahepatic biliary obstruction and normal livers were used as the control. Immunohistochemically, both MUC2 and MUC5AC were frequently expressed in mucinous ICC and IPNL, while expression of MUC2 was not seen in conventional ICC. The nuclear expression of CDX2 was closely associated with the expression of MUC2 in mucinous ICC and IPNL. This intimate association of MUC2 and CDX2 was confirmed by double immunostaining. The cytoplasmic CDX2 expression was frequent in the mucinous and the conventional ICC and pancreatic carcinoma, irrespective of MUC2 and MUC5AC expression. CDX2 mRNA was detected in neoplastic cells showing cytoplasmic as well as nuclear expression of CDX2 by reverse transcriptase-polymerase chain reaction. One IPMT expressed MUC2 associated with nuclear CDX2 expression, while the other IPMT and conventional pancreatic carcinoma expressed MUC5AC only. Aberrant expression of CDX2 is closely related to the overexpression of MUC2 in mucinous ICC and IPNL associated with hepatolithiasia, suggesting its role in intestinal differentiation and its association with carcinogenesis in these tumors.
authors.affiliation: Department of Human Pathology, Division of Surgical Oncology, Kanazawa University Graduate School of Medicine, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ishikawa
authors.forename: Motoko
authors.initials: M
authors.lastname: Sasaki
authors.forename: Shusaku
authors.initials: S
authors.lastname: Ohira
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
authors.forename: Koji
authors.initials: K
authors.lastname: Oda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nimura
authors.forename: Miin-Fu
authors.initials: MF
authors.lastname: Chen
authors.forename: Yi-Yin
authors.initials: YY
authors.lastname: Jan
authors.forename: Ta-Sen
authors.initials: TS
authors.lastname: Yeh
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology; D000071616:CDX2 Transcription Factor; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002769:Cholelithiasis / Q000150:complications*; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D008113:Liver Neoplasms / Q000150:complications* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D055271:Mucin 5AC; D055262:Mucin-2; D009077:Mucins / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators
chemical_list: D000071616:CDX2 Transcription Factor; D018076:DNA, Complementary; D018398:Homeodomain Proteins; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D055262:Mucin-2; D009077:Mucins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015534:Trans-Activators