التفاصيل البيبلوغرافية
| العنوان: |
An expression signature of the angiogenic response in gastrointestinal neuroendocrine tumours: correlation with tumour phenotype and survival outcomes. |
| المؤلفون: |
Pinato, D J, Tan, T M, Toussi, S T K, Ramachandran, R, Martin, N, Meeran, K, Ngo, N, Dina, R, Sharma, R |
| المصدر: |
British Journal of Cancer; 1/7/2014, Vol. 110 Issue 1, p115-122, 8p |
| مصطلحات موضوعية: |
NEOVASCULARIZATION, NEUROENDOCRINE tumors, GENE expression, PHENOTYPES, HEALTH outcome assessment, IMMUNOHISTOCHEMISTRY, GENETICS |
| مستخلص: |
Background:Gastroenteropancreatic 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.Methods:Tissue 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.Results:Eighty-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).Conclusion:We 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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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