title: Cripto-1 overexpression is involved in the tumorigenesis of gastric-type and pancreatobiliary-type intraductal papillary mucinous neoplasms of the pancreas.
abstract: Human Cripto-1, a membrane-bound protein, plays an important role during early embryogenesis and has oncogenic properties, including cell transformation and enhancement of invasion. Cripto-1 is up-regulated in various malignant tissues and premalignant lesions. However, Cripto-1 expression in intraductal papillary mucinous neoplasms (IPMNs) has yet to be reported. This study aimed to investigate Cripto-1 expression in IPMNs and evaluate the expression patterns according to the histological grade or phenotypic subclassification. Cripto-1 expression was evaluated by immunohistochemistry using 37 IPMN tissue samples and real-time RT-PCR analysis of seven frozen samples. Cripto-1 was up-regulated in 59.5% of IPMNs. Cripto-1 was positively stained in 3 of 4 (75%) adenomas, 12 of 19 (63.2%) borderline neoplasms, 5 of 11 (45.5%) non-invasive carcinomas and 2 of 3 (66.7%) invasive carcinomas. There was no correlation between Cripto-1 overexpression and the histological grade (P>0.05). Cripto-1 expression was significantly increased in pancreatobiliary- (4/5, 80%) and gastric-type (13/19, 68.4.2%) IPMNs compared with those of the intestinal type (2/10, 20%; P<0.01). Cripto-1 mRNA expression was higher in gastric- and pancreatobiliary-type IPMNs than in intestinal ones, supporting the immunohistochemical results. It is concluded that Cripto-1 overexpression is involved in the tumorigenesis of gastric- and pancreatobiliary-type IPMNs.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 120-752 Seoul, Korea.
authors.forename: Sung P
authors.initials: SP
authors.lastname: Hong
authors.forename: Eun K
authors.initials: EK
authors.lastname: Lee
authors.forename: Jeong Y
authors.initials: JY
authors.lastname: Park
authors.forename: Tae J
authors.initials: TJ
authors.lastname: Jeon
authors.forename: Seungmin
authors.initials: S
authors.lastname: Bang
authors.forename: Seungwoo
authors.initials: S
authors.lastname: Park
authors.forename: Jae B
authors.initials: JB
authors.lastname: Chung
authors.forename: Woo J
authors.initials: WJ
authors.lastname: Lee
authors.forename: Hoguen
authors.initials: H
authors.lastname: Kim
authors.forename: Si Y
authors.initials: SY
authors.lastname: Song
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000096:biosynthesis*; D005260:Female; D058851:GPI-Linked Proteins; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C070636:TDGF1 protein, human; D004815:Epidermal Growth Factor