Clinicopathological significance of altered Notch signaling in extrahepatic cholangiocarcinoma and gallbladder carcinoma

AIM：To investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 （DLL4） in extrahepatic cholangiocarcinoma and gallbladder carcinoma.METHODS：One hundred and ten patients had surgically resected extrahepatic cholangiocarcinoma （CC） and...

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Published in:World journal of gastroenterology : WJG 2011-09, Vol.17 (35), p.4023-4030
Main Authors: Yoon, Hyun Ah, Noh, Myung Hwan, Kim, Byung Geun, Han, Ji Sun, Jang, Jin Seok, Choi, Seok Ryeol, Jeong, Jin Sook, Chun, Jin Ho
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Animals
Brief
Cholangiocarcinoma - mortality
Cholangiocarcinoma - pathology
Cholangiocarcinoma - physiopathology
Disease Progression
Female
Gallbladder Neoplasms - mortality
Gallbladder Neoplasms - pathology
Gallbladder Neoplasms - physiopathology
Humans
Intercellular Signaling Peptides and Proteins - metabolism
Male
Middle Aged
Notch
Receptors, Notch - metabolism
Signal Transduction - physiology
Survival Rate
临床意义
免疫组织化学
受体蛋白
癌症
肝
胆囊
胆管
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Summary:AIM：To investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 （DLL4） in extrahepatic cholangiocarcinoma and gallbladder carcinoma.METHODS：One hundred and ten patients had surgically resected extrahepatic cholangiocarcinoma （CC） and gallbladder carcinoma specimens examined by immunohistochemistry of available paraffin blocks.Immunohistochemistry was performed using anti-Notch receptors 1-4 and anti-DLL4 antibodies.We scored the immunopositivity of Notch receptors and DLL4 expression by percentage of positive tumor cells with cytoplasmic expression and intensity of immunostaining.Coexistent nuclear localization was evaluated.Clinicopatho-logical parameters and survival data were compared with the expression of Notch receptors 1-4 and DLL4.RESULTS：Notch receptor proteins showed in the cytoplasm with or without nuclear expression in cancer cells,as well as showing weak cytoplasmic expression in non-neoplastic cells.By semiquantitative evaluation,positive immunostaining of Notch receptor 1 was detected in 96 cases （87.3%）,Notch receptor 2 in 97 （88.2%）,Notch receptor 3 in 97 （88.2%）,Notch receptor 4 in 103 （93.6）,and DLL4 in 84 （76.4%）.In addition,coex- istent nuclear localization was noted [Notch receptor 1;18 cases （18.8%）,Notch receptor 2;40 （41.2%）,Notch receptor 3;32 （33.0%）,Notch receptor 4;99 （96.1%）,DLL4;48 （57.1%）].Notch receptor 1 expression was correlated with advanced tumor,node,metastasis （TNM） stage （P=0.043）,Notch receptor 3 with advanced T stage （P=0.017）,tendency to express in cases with nodal metastasis （P=0.065） and advanced TNM stage （P=0.052）.DLL4 expression tended to be related to less histological differentiation （P=0.095）.Coexistent nuclear localization of Notch receptor 3 was related to no nodal metastasis （P=0.027） and Notch receptor 4 with less histological differentiation （P=0.036）,while DLL4 tended to be related inversely with T stage （P=0.053）.Coexistent nuclear localization of DLL4 was related to poor survival （P=0.002）.CONCLUSION：Aberrant expression of Notch receptors 1 and 3 play a role during cancer progression,and cytoplasmic nuclear coexistence of DLL4 expression correlates with poor survival in extrahepatic CC and gallbladder carcinoma.
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.v17.i35.4023