ArticleBritish journal of cancer2014
An expression signature of the angiogenic response in gastrointestinal neuroendocrine tumours: correlation with tumour phenotype and survival outcomes.
Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Bevacizumab-based combination therapy for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a systematic review of the literature.Journal of cancer research and clinical oncology · 2015Pooled it
- Review
- Intratumoral Heterogeneity of Ki67 Index and Its Impact on the Diagnosis and Prognostication of Pancreatic Neuroendocrine Tumors: Hot-Spot Count Differs Significantly from Random-Area Count.Endocrine pathology · 2025Article
- The Role of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Tumors.International journal of molecular sciences · 2025Review
- [Asia Oceania journal of nuclear medicine & biology · 2025Article
- Review
- Review
- Article
- Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy.Journal for immunotherapy of cancer · 2021Article
- Evaluation of SSTR2 Expression in SI-NETs and Relation to Overall Survival after PRRT.Cancers · 2021Article
- Update on Histological Reporting Changes in Neuroendocrine Neoplasms.Current oncology reports · 2021Review
- B7 immune-checkpoints as targets for the treatment of neuroendocrine tumors.Endocrine-related cancer · 2021Article
- PARP6 suppresses the proliferation and metastasis of hepatocellular carcinoma by degrading XRCC6 to regulate the Wnt/β-catenin pathway.American journal of cancer research · 2020Article
- A transcriptome-based signature of pathological angiogenesis predicts breast cancer patient survival.PLoS genetics · 2019Article
- HSP27 promotes epithelial-mesenchymal transition through activation of the β-catenin/MMP3 pathway in pancreatic ductal adenocarcinoma cells.Translational cancer research · 2019Article
- Integrated analysis of multiple receptor tyrosine kinases identifies Axl as a therapeutic target and mediator of resistance to sorafenib in hepatocellular carcinoma.British journal of cancer · 2019Article
- PEA15 promotes liver metastasis of colorectal cancer by upregulating the ERK/MAPK signaling pathway.Oncology reports · 2019Article
- Article
- Heat shock factor 1 inhibits the mitochondrial apoptosis pathway by regulating second mitochondria-derived activator of caspase to promote pancreatic tumorigenesis.Journal of experimental & clinical cancer research : CR · 2017Article
- Towards a new classification of gastroenteropancreatic neuroendocrine neoplasms.Nature reviews. Clinical oncology · 2016Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGastroenteropancreatic neuroendocrine tumours (GEP-NETs) are heterogeneous with respect to biological behaviour and prognosis. As angiogenesis is a renowned pathogenic hallmark as well as a therapeutic target, we aimed to investigate the prognostic and clinico-pathological role of tissue markers of hypoxia and angiogenesis in GEP-NETs.
methodsTissue microarray (TMA) blocks were constructed with 86 tumours diagnosed from 1988 to 2010. Tissue microarray sections were immunostained for hypoxia inducible factor 1α (Hif-1α), vascular endothelial growth factor-A (VEGF-A), carbonic anhydrase IX (Ca-IX) and somatostatin receptors (SSTR) 1-5, Ki-67 and CD31. Biomarker expression was correlated with clinico-pathological variables and tested for survival prediction using Kaplan-Meier and Cox regression methods.
resultsEighty-six consecutive cases were included: 51% male, median age 51 (range 16-82), 68% presenting with a pancreatic primary, 95% well differentiated, 51% metastatic. Higher grading (P=0.03), advanced stage (P<0.001), high Hif-1α and low SSTR-2 expression (P=0.03) predicted for shorter overall survival (OS) on univariate analyses. Stage, SSTR-2 and Hif-1α expression were confirmed as multivariate predictors of OS. Median OS for patients with SSTR-2+/Hif-1α-tumours was not reached after median follow up of 8.8 years, whereas SSTR-2-/Hif-1α+ GEP-NETs had a median survival of only 4.2 years (P=0.006).
conclusionWe have identified a coherent expression signature by immunohistochemistry that can be used for patient stratification and to optimise treatment decisions in GEP-NETs independently from stage and grading. Tumours with preserved SSTR-2 and low Hif-1α expression have an indolent phenotype and may be offered less aggressive management and less stringent follow up.
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