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Observational Study
. 2022 Apr;76(1):208-217.
doi: 10.1007/s12020-021-02942-4. Epub 2022 Jan 28.

Angiogenic factors as prognostic markers in neuroendocrine neoplasms

Giulia Puliani  1   2 , Franz Sesti  1 , Emanuela Anastasi  1 , Monica Verrico  3 , Maria Grazia Tarsitano  1 , Tiziana Feola  1   4 , Federica Campolo  1 , Cira Rosaria Tiziana Di Gioia  5 , Mary Anna Venneri  1 , Antonio Angeloni  1 , Marialuisa Appetecchia  2 , Andrea Lenzi  1 , Andrea Marcello Isidori  1 , Antongiulio Faggiano  6 , Elisa Giannetta  7 ; Nettare Unit
Collaborators, Affiliations
Observational Study

Angiogenic factors as prognostic markers in neuroendocrine neoplasms

Giulia Puliani et al. Endocrine. 2022 Apr.

Abstract

Purpose: Angiogenic markers in neuroendocrine neoplasms (NENs) have recently received increasing attention, but their clinical role remains unclear. The aim of this study was to evaluate the role of angiogenic markers in NEN aggressiveness and prognosis.

Methods: We performed a prospective observational study including 46 consecutive patients with proven NENs of pulmonary (45.65%) and gastro-entero-pancreatic (GEP) (54.35%) origin and 29 healthy controls. Circulating pro-angiogenic factors were measured by ELISA assay. ANG2 tissue expression was evaluated in a subgroup of ten patients by immunohistochemistry.

Results: The study demonstrated a significantly higher level of ANG2, ANG1, sTIE2, and PROK2 in patients affected by NENs compared to controls. In the NENs' group we measured that: (i) ANG2 levels were higher in poorly vs well-differentiated NENs: 4.85 (2.75-7.42) vs 3.16 (1.66-6.36) ng/ml, p = 0.046 and in tumor stage 3-4 compared to stage 1-2: 4.24 (2.66-8.72) vs 2.73 (1.53-5.70), p = 0.044; (ii) ANG2 and PROK2 were significantly higher in patents with progressive disease compared to stable disease: ANG2 = 6.26 (3.98-10.99) vs 2.73 (1.65-4.36) pg/ml, p = 0.001; PROK2 = 29.19 (28.42-32.25) vs 28.37 (28.14-28.91) pg/ml, p = 0.035. Immunohistochemistry confirmed ANG2 expression in tumor specimens.

Conclusions: We documented higher levels of angiogenic markers in NENs, with an association between ANG2 serum levels and NENs morphology and staging. In both GEP and lung NENs, ANG2 and PROK2 are higher in case of tumor progression, suggesting a potential role as prognostic markers in NENs patients.

Keywords: Angiogenesis; Angiopoietin; Neuroendocrine neoplasm; Neuroendocrine tumor; PROK2; Prognostic marker.

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