ECE2019 Poster Presentations Adrenal and Neuroendocrine Tumours 2 (60 abstracts)
Prognostic role of angiogenesis-associated factors Tie2 and Angiopoietin 2 in patients with neuroendocrine neoplasms: The NETTARE Unit experience
Giulia Puliani 1 , Franz Sesti 1 , Tiziana Feola 1 , Emilia Sbardella 1 , Alessia Cozzolino 1 , Riccardo Pofi 1 , Antongiulio Faggiano 1 , Andrea Lenzi 1 , Emanuela Anastasi 2 , Mary A Venneri 1 , Elisa Giannetta 1 & Andrea M Isidori 1
1Department of Experimental Medicine - ‘Sapienza’ University of Rome, Rome, Italy; 2Department of Molecular Medicine - ‘Sapienza’ University of Rome, Rome, Italy.
Introduction: The role of Angiopoietin (Ang)/Tie2 kinase pathway in neuroendocrine neoplasms (NENs) has recently received increasing attention, but its clinical role remains unclear. Tie2-receptor inactivation favours chronic inflammation. The balance between its agonist and antagonist regulates its signalling. Aim of this study was to measure serum soluble Tie2 (sTie2) and Ang-2 in patients followed at the NETTARE Unit (NeuroEndocrine TAsk foRcE of ‘Sapienza’ University).
Methods: A prospective observational study was carried out from June 2017 to December 2018 recruiting 43 consecutive patients with proven NENs (25 well-differentiated and 18 poorly-differentiated NENs) and 32 non-neoplastic controls (Ctrl) recruited among patients with thyroid disorders, matched for age, sex, BMI, smoking and comorbidities (diabetes mellitus, cardiovascular and inflammatory disorders). Serum levels of sTie2 and Ang-2 were determined by ELISA. Groups were compared using Mann-Whitney test.
Results: The mean age of the 43 NENs patients was 66.14±13.4 years (58.1% males) and tumour sites were: gastroenteropancreatic (GEP) NENs (53.5%), lung (39.5%), others (6.9%). Among GEP-NENs, most patients had a well-differentiated NENs (56.5% G1, 26.1% G2, 17.4% G3) and among lung NENs the majority were small and large cells carcinomas (72.2%). Locally advanced or metastatic disease (TNM stage III or IV) represented 66.6% of the sample. A positive correlation was found between Ang-2 and sTie2 levels in NENs patients (P=0.033), adjusted for age and sex. sTie2 (ng/ml) and Ang-2 (ng/ml) levels were significantly higher in NENs than controls (sTie2: NENs 53.67±34.72; Ctrl: 33.04±17.24, P=0.021; Ang-2: NENs 3.41±2.12; Ctrl: 1.45±1.39, P<0.001). Regarding grading, both sTie2 and Ang-2 were found higher in poorly differentiated NENs vs control (P=0.011 and P<0.001, respectively), while Ang-2 levels were also found higher in well-differentiated NENs vs control (P=0.007) and in poorly-differentiated vs well-differentiated NENs (P=0.009). Patients with locally advanced and metastatic disease exhibited higher Ang-2 levels than those with localized disease (stage III-IV 3.99±2.13; stage I-II 2.29±1.75, P=0.019). Compared to controls, Ang-2 levels were found higher in GEP-NENs (P=0.003), while both Ang-2 and sTie2 levels were found higher in lung NENs (P<0.001 and P=0.017, respectively).
Conclusions: The present study documents, prospectively, an association between NEN aggressiveness (staging and grading) and Ang/Tie2 inactivation. In both GEP and lung NENs, sTie2 and Ang-2 levels could play a role as novel additional markers for the diagnosis and prognosis of NENs.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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