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 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. Clinicopathological 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, coexistent 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2011 |
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| Erschienen: |
2011 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
World journal of gastroenterology - 17(2011), 35 vom: 21. Sept., Seite 4023-30 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yoon, Hyun Ah [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.01.2012 Date Revised 10.03.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.3748/wjg.v17.i35.4023 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM212681206 |
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| 041 | |a eng | ||
| 100 | 1 | |a Yoon, Hyun Ah |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Clinicopathological significance of altered Notch signaling in extrahepatic cholangiocarcinoma and gallbladder carcinoma |
| 264 | 1 | |c 2011 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 23.01.2012 | ||
| 500 | |a Date Revised 10.03.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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. Clinicopathological parameters and survival data were compared with the expression of Notch receptors 1-4 and DLL4 | ||
| 520 | |a 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, coexistent 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cholangiocarcinoma | |
| 650 | 4 | |a Delta-like ligand-4 | |
| 650 | 4 | |a Gallbladder carcinoma | |
| 650 | 4 | |a Immunohistochemistry | |
| 650 | 4 | |a Notch receptors | |
| 650 | 7 | |a Adaptor Proteins, Signal Transducing |2 NLM | |
| 650 | 7 | |a Calcium-Binding Proteins |2 NLM | |
| 650 | 7 | |a DLL4 protein, human |2 NLM | |
| 650 | 7 | |a Intercellular Signaling Peptides and Proteins |2 NLM | |
| 650 | 7 | |a Receptors, Notch |2 NLM | |
| 700 | 1 | |a Noh, Myung Hwan |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Byung Geun |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Ji Sun |e verfasserin |4 aut | |
| 700 | 1 | |a Jang, Jin Seok |e verfasserin |4 aut | |
| 700 | 1 | |a Choi, Seok Ryeol |e verfasserin |4 aut | |
| 700 | 1 | |a Jeong, Jin Sook |e verfasserin |4 aut | |
| 700 | 1 | |a Chun, Jin Ho |e verfasserin |4 aut | |
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