Clinicopathologic significance of the delta-like ligand 4, vascular endothelial growth factor, and hypoxia-inducible factor-2α in gallbladder cancer
Background Gallbladder cancer (GBC) is usually detected in advanced stages with a low 5-year survival rate. Delta-like ligand 4 (DLL4), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-2alpha (HIF2α) have been studied for their role in tumorigenesis and potential for therapeut...
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| Format: | Article |
| Language: | English |
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Korean Society of Pathologists & the Korean Society for Cytopathology
2023-03-01
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| Series: | Journal of Pathology and Translational Medicine |
| Subjects: | |
| Online Access: | http://jpatholtm.org/upload/pdf/jptm-2023-02-01.pdf |
| _version_ | 1797867219932151808 |
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| author | Sujin Park Junsik Kim Woncheol Jang Kyoung-Mee Kim Kee-Taek Jang |
| author_facet | Sujin Park Junsik Kim Woncheol Jang Kyoung-Mee Kim Kee-Taek Jang |
| author_sort | Sujin Park |
| collection | DOAJ |
| description | Background Gallbladder cancer (GBC) is usually detected in advanced stages with a low 5-year survival rate. Delta-like ligand 4 (DLL4), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-2alpha (HIF2α) have been studied for their role in tumorigenesis and potential for therapeutic target, and multiple clinical trials of the agents targeting them are ongoing. We investigated the expression of these markers in surgically resected GBC and tried to reveal their association with the clinicopathologic features, mutual correlation of their expression, and prognosis of the GBC patients by their expression. Methods We constructed the tissue microarray blocks of 99 surgically resected GBC specimens and performed immunohistochemistry of DLL4, VEGF, and HIF2α. We used the quantitative digital image analysis to evaluate DLL4 and VEGF expression, while the expression of HIF2α was scored manually. Results The expression of VEGF and HIF2α showed a significant trend with tumor differentiation (p = .028 and p = .006, respectively). We found that the high DLL4 and VEGF expression were significantly correlated with lymph node metastasis (p = .047, both). The expression of VEGF and HIF2α were significantly correlated (p < .001). The GBC patients with low HIF2α expression showed shorter recurrence-free survival than those with high HIF2α expression. Conclusions This study suggested the possibility of the usage of DLL4 and VEGF to predict the lymph node metastasis and the possibility of VEGF and HIF2α to predict the expression level mutually. Further studies may be needed to validate our study results and eventually accelerate the introduction of the targeted therapy in GBC. |
| first_indexed | 2024-04-09T23:36:50Z |
| format | Article |
| id | doaj.art-007761423497425680dee7b6fed4a9da |
| institution | Directory Open Access Journal |
| issn | 2383-7837 2383-7845 |
| language | English |
| last_indexed | 2024-04-09T23:36:50Z |
| publishDate | 2023-03-01 |
| publisher | Korean Society of Pathologists & the Korean Society for Cytopathology |
| record_format | Article |
| series | Journal of Pathology and Translational Medicine |
| spelling | doaj.art-007761423497425680dee7b6fed4a9da2023-03-20T04:41:41ZengKorean Society of Pathologists & the Korean Society for CytopathologyJournal of Pathology and Translational Medicine2383-78372383-78452023-03-0157211312210.4132/jptm.2023.02.0117064Clinicopathologic significance of the delta-like ligand 4, vascular endothelial growth factor, and hypoxia-inducible factor-2α in gallbladder cancerSujin Park0Junsik Kim1Woncheol Jang2Kyoung-Mee Kim3Kee-Taek Jang4 Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Department of Statistics, Duksung Women’s University, Seoul, Korea Department of Statistics, Duksung Women’s University, Seoul, Korea Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaBackground Gallbladder cancer (GBC) is usually detected in advanced stages with a low 5-year survival rate. Delta-like ligand 4 (DLL4), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-2alpha (HIF2α) have been studied for their role in tumorigenesis and potential for therapeutic target, and multiple clinical trials of the agents targeting them are ongoing. We investigated the expression of these markers in surgically resected GBC and tried to reveal their association with the clinicopathologic features, mutual correlation of their expression, and prognosis of the GBC patients by their expression. Methods We constructed the tissue microarray blocks of 99 surgically resected GBC specimens and performed immunohistochemistry of DLL4, VEGF, and HIF2α. We used the quantitative digital image analysis to evaluate DLL4 and VEGF expression, while the expression of HIF2α was scored manually. Results The expression of VEGF and HIF2α showed a significant trend with tumor differentiation (p = .028 and p = .006, respectively). We found that the high DLL4 and VEGF expression were significantly correlated with lymph node metastasis (p = .047, both). The expression of VEGF and HIF2α were significantly correlated (p < .001). The GBC patients with low HIF2α expression showed shorter recurrence-free survival than those with high HIF2α expression. Conclusions This study suggested the possibility of the usage of DLL4 and VEGF to predict the lymph node metastasis and the possibility of VEGF and HIF2α to predict the expression level mutually. Further studies may be needed to validate our study results and eventually accelerate the introduction of the targeted therapy in GBC.http://jpatholtm.org/upload/pdf/jptm-2023-02-01.pdfgallbladder neoplasmsdll4vascular endothelial growth factorhif2αtargeted therapy |
| spellingShingle | Sujin Park Junsik Kim Woncheol Jang Kyoung-Mee Kim Kee-Taek Jang Clinicopathologic significance of the delta-like ligand 4, vascular endothelial growth factor, and hypoxia-inducible factor-2α in gallbladder cancer Journal of Pathology and Translational Medicine gallbladder neoplasms dll4 vascular endothelial growth factor hif2α targeted therapy |
| title | Clinicopathologic significance of the delta-like ligand 4, vascular endothelial growth factor, and hypoxia-inducible factor-2α in gallbladder cancer |
| title_full | Clinicopathologic significance of the delta-like ligand 4, vascular endothelial growth factor, and hypoxia-inducible factor-2α in gallbladder cancer |
| title_fullStr | Clinicopathologic significance of the delta-like ligand 4, vascular endothelial growth factor, and hypoxia-inducible factor-2α in gallbladder cancer |
| title_full_unstemmed | Clinicopathologic significance of the delta-like ligand 4, vascular endothelial growth factor, and hypoxia-inducible factor-2α in gallbladder cancer |
| title_short | Clinicopathologic significance of the delta-like ligand 4, vascular endothelial growth factor, and hypoxia-inducible factor-2α in gallbladder cancer |
| title_sort | clinicopathologic significance of the delta like ligand 4 vascular endothelial growth factor and hypoxia inducible factor 2α in gallbladder cancer |
| topic | gallbladder neoplasms dll4 vascular endothelial growth factor hif2α targeted therapy |
| url | http://jpatholtm.org/upload/pdf/jptm-2023-02-01.pdf |
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