Biomarkers and receptor expression in neuroendocrine tumours.
Doctoral thesis, UCL (University College London).
Neuroendocrine tumours (NETs) are uncommon tumours which have a diverse biology. The aims of this thesis were to identify potential new biomarkers and further develop understanding of tumour biology in NETs. The following were assessed i) somatostatin receptor (SSTR) and dopamine-2 receptor (D2R) expression in NETs, ii)HER expression and their associated prognosis, iii) Angiopoietin expression in NETs and their prognostic significance, iv) proteomic analysis of serum and NET cell lines to identify novel markers and finally v) the role of 68Ga-DOTATATE PET in imaging of NETs. Immunohistochemical studies were performed to determine whether SSTR and D2R are co-expressed in NETs. D2R was co-expressed with SSTR-2 and -5 in 93% of low grade tumours, with lower co-expression in higher grade tumours. HER family of receptors are involved in oncogenesis; the expressions of these receptors were assessed. Immunohistochemical analysis of these receptors was performed in 82 cases. EGFR was expressed in 86%, HER-2 0%, HER-3 8.5% and HER-4 91.5%. The expression of EGFR was not associated with poor prognosis. Angiopoietins (Ang) are involved in tumourogenesis. Serum Ang-1 and Ang-2 were measured in patients and healthy controls. Ang-2 was significantly higher in patients compared to controls. Patients with Ang-2 levels >4756pg/ml had a shorter time to progression. Proteomic analysis using gel electrophoresis and LC/MS/MS of plasma from NET patients and established NET cell lines was performed to identify biomarkers. Proteomic cell line analysis identified 17 proteins in all cell lines including Mac-2 binding protein. We validated Mac-2 binding protein and it appears to be a potential marker for NETs. Finally, we performed a study to ascertain whether 68Ga-DOTATATE PET identifies more lesions in NET patients in whom 111In-DTPA-Octreotide showed faint/negative lesion uptake. 111In-DTPA-Octreotide scintigraphy identified 27 lesions compared to 168 lesions identified with Ga-68-DOTATATE PET. 68Ga-DOTATATE PET is a sensitive imaging modality for identifying NETs.
|Title:||Biomarkers and receptor expression in neuroendocrine tumours|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Internal Medicine|
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