title: Clinicopathological significance of aberrant Notch receptors in intrahepatic cholangiocarcinoma.
abstract: Notch signaling has been reported to be activated to promote biliary epithelial cell differentiation and tubulogenesis during bile duct development. In this study, clinicopathological significance of aberrant expression of Notch receptors in intrahepatic cholangiocarcinoma (ICC) was investigated. Thus, forty-one ICC specimens were examined by immunohistochemistry using anti-Notch1-4 antibodies, respectively. Expression of Notch receptors was scored by percentage of positive tumor cells and intensity of immunostaining. Clinicopathological parameters and survival data were compared with the expression of Notch receptors, respectively. Expression of Notch receptors was identified in cancer cells, as well as in non-neoplastic cells. Compared with adjacent non-tumor liver tissues, Notch1 and 4 were up regulated, and Notch2 and 3 were relatively weaker. Positive immunostaining of Notch1 in ICC cells was detected in 34 cases (82.9%), Notch2 in 23 (56.1%), Notch3 in 16 (39.0%) and Notch4 in 14 (34.1%). Notch1 was overexpressed in cases with tumor size > 5 cm (P = 0.036). Expression of Notch2 was correlated inversely with histological grade (P = 0.016). Overexpression of Notch4 was more common in cases with serum CA125 > 35 U/ml than cases with CA125 ≤ 35 U/ml (P = 0.048). Expression of Notch3 was not correlated with any other clinicopathological parameters. Moreover, Notch4 was related to poor survival (P < 0.001). To conclude, this study reveals that aberrant expression of Notch receptors 1 and 4 might play important roles during ICC progression.
authors.affiliation: Department of Hepato-Pancreato-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, Guangdong Province, China.
authors.forename: Wen-Rui
authors.initials: WR
authors.lastname: Wu
authors.affiliation: Department of Hepato-Pancreato-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, Guangdong Province, China.
authors.forename: Xiang-De
authors.initials: XD
authors.lastname: Shi
authors.affiliation: Department of Hepato-Pancreato-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, Guangdong Province, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Hepato-Pancreato-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, Guangdong Province, China.
authors.forename: Man-Sheng
authors.initials: MS
authors.lastname: Zhu
authors.affiliation: Department of Hepato-Pancreato-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, Guangdong Province, China.
authors.forename: Lei-Bo
authors.initials: LB
authors.lastname: Xu
authors.affiliation: Department of Hepato-Pancreato-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, Guangdong Province, China.
authors.forename: Xian-Huan
authors.initials: XH
authors.lastname: Yu
authors.affiliation: Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, Guangdong Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Department of Hepato-Pancreato-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, Guangdong Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Hepato-Pancreato-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou 510120, Guangdong Province, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D018281:Cholangiocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D051880:Receptors, Notch / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D051880:Receptors, Notch
keywords: Intrahepatic cholangiocarcinoma; Notch receptors; immunohistochemistry