Skip to main content

Advertisement

SpringerLink
Log in

Angiogenic factors as prognostic markers in neuroendocrine neoplasms

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

Data are available from the authors.

Abbreviations

NEN:

neuroendocrine neoplasm

NET:

neuroendocrine tumor

NEC:

neuroendocrine carcinoma

GEP:

gastro-entero-pancreatic

ANG:

angiopoietin

SSA:

somatostatin analogs

VEGF:

vascular endothelial growth factor

PROK:

prokineticins

PROKR:

prokineticins receptor

sTIE2:

soluble TIE2

SD:

standard deviation

References

  1. J. Hallet, C.H. Law, M. Cukier, R. Saskin, N. Liu, S. Singh, Exploring the rising incidence of neuroendocrine tumors: a population-based analysis of epidemiology, metastatic presentation, and outcomes. Cancer 121(4), 589–597 (2015). https://doi.org/10.1002/cncr.29099

    Article  PubMed  Google Scholar 

  2. A. Dasari, C. Shen, D. Halperin, B. Zhao, S. Zhou, Y. Xu et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol. 3(10), 1335–1342 (2017). https://doi.org/10.1001/jamaoncol.2017.0589

    Article  PubMed  PubMed Central  Google Scholar 

  3. K.I. Alexandraki, M. Tsoli, G. Kyriakopoulos, A. Angelousi, G. Nikolopoulos, D. Kolomodi et al. Current concepts in the diagnosis and management of neuroendocrine neoplasms of unknown primary origin. Minerva Endocrinol. 44(4), 378–386 (2019). https://doi.org/10.23736/S0391-1977.19.03012-8

    Article  PubMed  Google Scholar 

  4. G. Gaudenzi, A. Dicitore, S. Carra, D. Saronni, C. Pozza, E. Giannetta et al. MANAGEMENT OF ENDOCRINE DISEASE: precision medicine in neuroendocrine neoplasms: an update on current management and future perspectives. Eur. J. Endocrinol. 181(1), R1–R10 (2019). https://doi.org/10.1530/EJE-19-0021

    Article  CAS  PubMed  Google Scholar 

  5. A. Couvelard, D. O’Toole, H. Turley, R. Leek, A. Sauvanet, C. Degott et al. Microvascular density and hypoxia-inducible factor pathway in pancreatic endocrine tumours: negative correlation of microvascular density and VEGF expression with tumour progression. Br. J. Cancer 92(1), 94–101 (2005). https://doi.org/10.1038/sj.bjc.6602245

    Article  CAS  PubMed  Google Scholar 

  6. M. Theodoropoulou, G.K. Stalla, Somatostatin receptors: from signaling to clinical practice. Front. Neuroendocrinol. 34(3), 228–252 (2013). https://doi.org/10.1016/j.yfrne.2013.07.005

    Article  CAS  PubMed  Google Scholar 

  7. C. Viallard, B. Larrivee, Tumor angiogenesis and vascular normalization: alternative therapeutic targets. Angiogenesis 20(4), 409–426 (2017). https://doi.org/10.1007/s10456-017-9562-9

    Article  CAS  PubMed  Google Scholar 

  8. M. Thomas, H.G. Augustin, The role of the Angiopoietins in vascular morphogenesis. Angiogenesis 12(2), 125–137 (2009). https://doi.org/10.1007/s10456-009-9147-3

    Article  CAS  PubMed  Google Scholar 

  9. D. Chakroborty, C. Sarkar, H. Yu, J. Wang, Z. Liu, P.S. Dasgupta et al. Dopamine stabilizes tumor blood vessels by up-regulating angiopoietin 1 expression in pericytes and Kruppel-like factor-2 expression in tumor endothelial cells. Proc. Natl Acad. Sci. USA. 108(51), 20730–20735 (2011). https://doi.org/10.1073/pnas.1108696108

    Article  PubMed  PubMed Central  Google Scholar 

  10. J. Holash, S.J. Wiegand, G.D. Yancopoulos, New model of tumor angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF. Oncogene 18(38), 5356–5362 (1999). https://doi.org/10.1038/sj.onc.1203035

    Article  CAS  PubMed  Google Scholar 

  11. H.G. Augustin, G.Y. Koh, G. Thurston, K. Alitalo, Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat. Rev. Mol. Cell. Biol. 10(3), 165–177 (2009). https://doi.org/10.1038/nrm2639

    Article  CAS  PubMed  Google Scholar 

  12. L. Negri, R. Lattanzi, E. Giannini, P. Melchiorri, Bv8/Prokineticin proteins and their receptors. Life Sci. 81(14), 1103–1116 (2007). https://doi.org/10.1016/j.lfs.2007.08.011

    Article  CAS  PubMed  Google Scholar 

  13. E.S. Ngan, P.K. Tam, Prokineticin-signaling pathway. Int. J. Biochem. Cell. Biol. 40(9), 1679–1684 (2008). https://doi.org/10.1016/j.biocel.2008.03.010

    Article  CAS  PubMed  Google Scholar 

  14. Y. Zhao, J. Wu, X. Wang, H. Jia, D.N. Chen, J.D. Li, Prokineticins and their G protein-coupled receptors in health and disease. Prog. Mol. Biol. Transl. Sci. 161, 149–179 (2019). https://doi.org/10.1016/bs.pmbts.2018.09.006

    Article  CAS  PubMed  Google Scholar 

  15. N. Figueroa-Vega, A. Diaz, M. Adrados, C. Alvarez-Escola, A. Paniagua, J. Aragones et al. The association of the angiopoietin/Tie-2 system with the development of metastasis and leukocyte migration in neuroendocrine tumors. Endocr. Relat. Cancer 17(4), 897–908 (2010). https://doi.org/10.1677/ERC-10-0020

    Article  CAS  PubMed  Google Scholar 

  16. A.S. Corlan, A.M. Cimpean, A.A. Jitariu, E. Melnic, M. Raica, Endocrine gland-derived vascular endothelial growth factor/prokineticin-1 in cancer development and tumor angiogenesis. Int. J. Endocrinol. 2017, 3232905 (2017). https://doi.org/10.1155/2017/3232905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. R. Rust, C. Gantner, M.E. Schwab, Pro- and antiangiogenic therapies: current status and clinical implications. FASEB J. 33(1), 34–48 (2019). https://doi.org/10.1096/fj.201800640RR

    Article  CAS  PubMed  Google Scholar 

  18. H. Choi, A. Moon, Crosstalk between cancer cells and endothelial cells: implications for tumor progression and intervention. Arch. Pharm. Res. 41(7), 711–724 (2018). https://doi.org/10.1007/s12272-018-1051-1

    Article  CAS  PubMed  Google Scholar 

  19. J. Folkman, Tumor angiogenesis. Adv. Cancer Res. 19, 331–358 (1974). https://doi.org/10.1016/s0065-230x(08)60058-5

    Article  CAS  PubMed  Google Scholar 

  20. R.I. Teleanu, C. Chircov, A.M. Grumezescu, D.M. Teleanu. Tumor angiogenesis and anti-angiogenic strategies for cancer treatment. J. Clin. Med. 9(1), 84 (2020). https://doi.org/10.3390/jcm9010084.

  21. A.M. Isidori, M.A. Venneri, D. Fiore, Angiopoietin-1 and Angiopoietin-2 in metabolic disorders: therapeutic strategies to restore the highs and lows of angiogenesis in diabetes. J. Endocrinol. Invest. 39(11), 1235–1246 (2016). https://doi.org/10.1007/s40618-016-0502-0

    Article  CAS  PubMed  Google Scholar 

  22. M.A. Venneri, F. Barbagallo, D. Fiore, R. De Gaetano, E. Giannetta, E. Sbardella et al. PDE5 inhibition stimulates Tie2-expressing monocytes and Angiopoietin-1 restoring angiogenic homeostasis in diabetes. J. Clin. Endocrinol. Metab. 104(7), 2623–2636 (2019). https://doi.org/10.1210/jc.2018-02525

    Article  PubMed  Google Scholar 

  23. R. Lorbeer, S.E. Baumeister, M. Dorr, S.B. Felix, M. Nauck, A. Grotevendt et al. Angiopoietin-2, its soluble receptor Tie-2 and subclinical cardiovascular disease in a population-based sample. Heart 101(3), 178–184 (2015). https://doi.org/10.1136/heartjnl-2014-306056

    Article  CAS  PubMed  Google Scholar 

  24. M. Whitehead, A. Osborne, P.S. Widdowson, P. Yu-Wai-Man, K.R. Martin, Angiopoietins in diabetic retinopathy: current understanding and therapeutic potential. J. Diabetes Res. 2019, 5140521 (2019). https://doi.org/10.1155/2019/5140521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. J. Sahni, S.S. Patel, P.U. Dugel, A.M. Khanani, C.D. Jhaveri, C.C. Wykoff et al. Simultaneous inhibition of Angiopoietin-2 and vascular endothelial growth factor-A with faricimab in diabetic macular edema: BOULEVARD Phase 2 Randomized Trial. Ophthalmology 126(8), 1155–1170 (2019). https://doi.org/10.1016/j.ophtha.2019.03.023

    Article  PubMed  Google Scholar 

  26. H. Huang, A. Bhat, G. Woodnutt, R. Lappe, Targeting the ANGPT-TIE2 pathway in malignancy. Nat. Rev. Cancer 10(8), 575–585 (2010). https://doi.org/10.1038/nrc2894

    Article  CAS  PubMed  Google Scholar 

  27. L. Hakanpaa, T. Sipila, V.M. Leppanen, P. Gautam, H. Nurmi, G. Jacquemet et al. Endothelial destabilization by angiopoietin-2 via integrin beta1 activation. Nat. Commun. 6, 5962 (2015). https://doi.org/10.1038/ncomms6962

    Article  CAS  PubMed  Google Scholar 

  28. K.M. Detjen, S. Rieke, A. Deters, P. Schulz, A. Rexin, S. Vollmer et al. Angiopoietin-2 promotes disease progression of neuroendocrine tumors. Clin. Cancer Res. 16(2), 420–429 (2010). https://doi.org/10.1158/1078-0432.CCR-09-1924

    Article  CAS  PubMed  Google Scholar 

  29. R. Srirajaskanthan, G. Dancey, A. Hackshaw, T. Luong, M.E. Caplin, T. Meyer, Circulating angiopoietin-2 is elevated in patients with neuroendocrine tumours and correlates with disease burden and prognosis. Endocr. Relat. Cancer 16(3), 967–976 (2009). https://doi.org/10.1677/ERC-09-0089

    Article  CAS  PubMed  Google Scholar 

  30. G. Melen-Mucha, A. Niedziela, S. Mucha, E. Motylewska, H. Lawnicka, J. Komorowski et al. Elevated peripheral blood plasma concentrations of tie-2 and angiopoietin 2 in patients with neuroendocrine tumors. Int. J. Mol. Sci. 13(2), 1444–1460 (2012). https://doi.org/10.3390/ijms13021444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. J. LeCouter, J. Kowalski, J. Foster, P. Hass, Z. Zhang, L. Dillard-Telm et al. Identification of an angiogenic mitogen selective for endocrine gland endothelium. Nature 412(6850), 877–884 (2001). https://doi.org/10.1038/35091000

    Article  CAS  PubMed  Google Scholar 

  32. M. Li, C.M. Bullock, D.J. Knauer, F.J. Ehlert, Q.Y. Zhou, Identification of two prokineticin cDNAs: recombinant proteins potently contract gastrointestinal smooth muscle. Mol. Pharmacol. 59(4), 692–698 (2001). https://doi.org/10.1124/mol.59.4.692

    Article  CAS  PubMed  Google Scholar 

  33. F.A. Ferrer, L.J. Miller, R.I. Andrawis, S.H. Kurtzman, P.C. Albertsen, V.P. Laudone et al. Angiogenesis and prostate cancer: in vivo and in vitro expression of angiogenesis factors by prostate cancer cells. Urology 51(1), 161–167 (1998). https://doi.org/10.1016/s0090-4295(97)00491-3

    Article  CAS  PubMed  Google Scholar 

  34. T. Goi, M. Fujioka, Y. Satoh, S. Tabata, K. Koneri, H. Nagano et al. Angiogenesis and tumor proliferation/metastasis of human colorectal cancer cell line SW620 transfected with endocrine glands-derived-vascular endothelial growth factor, as a new angiogenic factor. Cancer Res. 64(6), 1906–1910 (2004). https://doi.org/10.1158/0008-5472.can-3696-2

    Article  CAS  PubMed  Google Scholar 

  35. D. Pasquali, V. Rossi, S. Staibano, G. De Rosa, P. Chieffi, D. Prezioso et al. The endocrine-gland-derived vascular endothelial growth factor (EG-VEGF)/prokineticin 1 and 2 and receptor expression in human prostate: up-regulation of EG-VEGF/prokineticin 1 with malignancy. Endocrinology 147(9), 4245–4251 (2006). https://doi.org/10.1210/en.2006-0614

    Article  CAS  PubMed  Google Scholar 

  36. J. Monnier, M. Samson, Prokineticins in angiogenesis and cancer. Cancer Lett. 296(2), 144–149 (2010). https://doi.org/10.1016/j.canlet.2010.06.011

    Article  CAS  PubMed  Google Scholar 

  37. N. Ferrara, Role of myeloid cells in vascular endothelial growth factor-independent tumor angiogenesis. Curr. Opin. Hematol. 17(3), 219–224 (2010). https://doi.org/10.1097/MOH.0b013e3283386660

    Article  CAS  PubMed  Google Scholar 

  38. Y. Wang, X. Guo, H. Ma, L. Lu, R. Zhang, Prokineticin-2 is associated with metabolic syndrome in a middle-aged and elderly Chinese population. Lipids Health Dis. 15, 1 (2016). https://doi.org/10.1186/s12944-015-0172-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. T. Schirinzi, D. Maftei, M. Pieri, S. Bernardini, N.B. Mercuri, R. Lattanzi et al. Increase of Prokineticin-2 in serum of patients with Parkinson’s disease. Mov. Disord. 36(4), 1031–1033 (2021). https://doi.org/10.1002/mds.28458

    Article  CAS  PubMed  Google Scholar 

  40. T. Collot, J.D. Fumet, Q. Klopfenstein, J. Vincent, L. Bengrine, F. Ghiringhelli, Bevacizumab-based chemotherapy for poorly-differentiated neuroendocrine tumors. Anticancer Res. 38(10), 5963–5968 (2018). https://doi.org/10.21873/anticanres.12943

    Article  CAS  PubMed  Google Scholar 

  41. J.C. Yao, A. Phan, P.M. Hoff, H.X. Chen, C. Charnsangavej, S.C. Yeung et al. Targeting vascular endothelial growth factor in advanced carcinoid tumor: a random assignment phase II study of depot octreotide with bevacizumab and pegylated interferon alpha-2b. J. Clin. Oncol. 26(8), 1316–1323 (2008). https://doi.org/10.1200/JCO.2007.13.6374

    Article  CAS  PubMed  Google Scholar 

  42. J.C. Yao, K.A. Guthrie, C. Moran, J.R. Strosberg, M.H. Kulke, J.A. Chan et al. Phase III prospective randomized comparison trial of depot octreotide plus interferon Alfa-2b versus depot octreotide plus bevacizumab in patients with advanced carcinoid tumors: SWOG S0518. J. Clin. Oncol. 35(15), 1695–1703 (2017). https://doi.org/10.1200/JCO.2016.70.4072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. M. Kulke, D. Niedzwiecki, N.R. Foster, B. Fruth, P. Kunz, H. Kennecke et al. Randomized phase II study of everolimus (E) versus everolimus plus bevacizumab (E+B) in patients (Pts) with locally advanced or metastatic pancreatic neuroendocrine tumors (pNET), CALGB 80701 (Alliance). J. Clin. Oncol. 33, 2015 (2015).

    Article  Google Scholar 

  44. J. Gillen, D. Richardson, K. Moore, Angiopoietin-1 and Angiopoietin-2 inhibitors: clinical development. Curr. Oncol. Rep. 21(3), 22 (2019). https://doi.org/10.1007/s11912-019-0771-9

    Article  PubMed  Google Scholar 

  45. N. Rigamonti, E. Kadioglu, I. Keklikoglou, C. Wyser Rmili, C.C. Leow, M. De Palma, Role of angiopoietin-2 in adaptive tumor resistance to VEGF signaling blockade. Cell. Rep. 8(3), 696–706 (2014). https://doi.org/10.1016/j.celrep.2014.06.059

    Article  CAS  PubMed  Google Scholar 

  46. V. Baeriswyl, G. Christofori, The angiogenic switch in carcinogenesis. Semin. Cancer Biol. 19(5), 329–337 (2009). https://doi.org/10.1016/j.semcancer.2009.05.003

    Article  CAS  PubMed  Google Scholar 

  47. K. Oberg, E. Krenning, A. Sundin, L. Bodei, M. Kidd, M. Tesselaar et al. A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management. Endocr. Connect. 5(5), 174–187 (2016). https://doi.org/10.1530/EC-16-0043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work has been supported by the NETTARE Unit of Sapienza University. We would like to acknowledge all the members: Domenico Alvaro, Emanuela Anastasi, Antonio Angeloni, Oreste Bagni, Caterina Bangrazi, Massimiliano Bassi, Mario Bezzi, Nadia Bulzonetti, Vito Cantisani, Roberto Caronna, Giovanni Casella, Carlo Catalano, Roberta Centello, Enrico Cortesi, Ferdinando D’Ambrosio, Carlo Della Rocca, Adriano De Santis, Cira Di Gioia, Valentina Di Vito, Antongiulio Faggiano, Tiziana Feola, Daniele Gianfrilli, Alfredo Genco, Elisa Giannetta, Franco Iafrate, Andrea M. Isidori, Andrea Lenzi, Paolo Marchetti, Francesca Maccioni, Giulia Puliani, Carla Pandozzi, Franz Sesti, Carola Severi, Silverio Tomao, Vincenzo Tombolini, Federico Venuta, Monica Verrico.

Nettare Unit

Domenico Alvaro7, Emanuela Anastasi1, Antonio Angeloni1, Oreste Bagni8, Caterina Bangrazi9, Massimiliano Bassi10, Mario Bezzi11, Nadia Bulzonetti9, Vito Cantisani5, Roberto Caronna12, Giovanni Casella12, Carlo Catalano5, Roberta Centello1, Enrico Cortesi13, Ferdinando D’Ambrosio5, Carlo Della Rocca5, Adriano De Santis7, Cira Rosaria Tiziana Di Gioia5, Valentina Di Vito1, Antongiulio Faggiano6, Tiziana Feola1,4, Daniele Gianfrilli1, Alfredo Genco12, Elisa Giannetta1, Franco Iafrate5, Andrea M. Isidori1, Andrea Lenzi1, Paolo Marchetti13, Francesca Maccioni5, Alessio Molfino14, Maurizio Muscaritoli14, Carla Pandozzi1, Giulia Puliani1,2, Franz Sesti1, Carola Severi7, Silverio Tomao3, Vincenzo Tombolini9, Federico Venuta10, Monica Verrico3

Funding

This work was supported by the Ministerial research project PRIN2017Z3N3YC and Sapienza University Research Grant RM120172ADA2C4AF.

Author information

Authors and Affiliations

  1. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

    Giulia Puliani, Franz Sesti, Emanuela Anastasi, Maria Grazia Tarsitano, Tiziana Feola, Federica Campolo, Mary Anna Venneri, Antonio Angeloni, Andrea Lenzi, Andrea Marcello Isidori, Elisa Giannetta, Emanuela Anastasi, Antonio Angeloni, Roberta Centello, Valentina Di Vito, Tiziana Feola, Daniele Gianfrilli, Elisa Giannetta, Andrea M. Isidori, Andrea Lenzi, Carla Pandozzi, Giulia Puliani & Franz Sesti

  2. Oncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy

    Giulia Puliani, Marialuisa Appetecchia & Giulia Puliani

  3. Medical Oncology Unit A, Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy

    Monica Verrico, Silverio Tomao & Monica Verrico

  4. Neuroendocrinology, Neuromed Institute, IRCCS, Pozzilli, Italy

    Tiziana Feola & Tiziana Feola

  5. Department of Radiological, Anatomopathological and Oncological Sciences, Sapienza University of Rome, Rome, Italy

    Cira Rosaria Tiziana Di Gioia, Vito Cantisani, Carlo Catalano, Ferdinando D’Ambrosio, Carlo Della Rocca, Cira Rosaria Tiziana Di Gioia, Franco Iafrate & Francesca Maccioni

  6. Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy

    Antongiulio Faggiano & Antongiulio Faggiano

  7. Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

    Domenico Alvaro, Adriano De Santis & Carola Severi

  8. Department of Nuclear Medicine, Santa Maria Goretti Hospital, Latina, Italy

    Oreste Bagni

  9. Department of Radiation Oncology, Sapienza University of Rome, Rome, Italy

    Caterina Bangrazi, Nadia Bulzonetti & Vincenzo Tombolini

  10. Department of Thoracic Surgery, Sapienza University of Rome, Rome, Italy

    Massimiliano Bassi & Federico Venuta

  11. Vascular and Interventional Radiology Unit, Department of Diagnostic Service, Sapienza University of Rome, Rome, Italy

    Mario Bezzi

  12. Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy

    Roberto Caronna, Giovanni Casella & Alfredo Genco

  13. Medical Oncology Unit B, Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy

    Enrico Cortesi & Paolo Marchetti

  14. Department of Translational Medicine, Sapienza University of Rome, Rome, Italy

    Alessio Molfino & Maurizio Muscaritoli

Authors
  1. Giulia Puliani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Franz Sesti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emanuela Anastasi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Monica Verrico
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria Grazia Tarsitano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tiziana Feola
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Federica Campolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Cira Rosaria Tiziana Di Gioia
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mary Anna Venneri
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Antonio Angeloni
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Marialuisa Appetecchia
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Andrea Lenzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Andrea Marcello Isidori
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Antongiulio Faggiano
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Elisa Giannetta
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of Nettare Unit

  • Domenico Alvaro
  • , Emanuela Anastasi
  • , Antonio Angeloni
  • , Oreste Bagni
  • , Caterina Bangrazi
  • , Massimiliano Bassi
  • , Mario Bezzi
  • , Nadia Bulzonetti
  • , Vito Cantisani
  • , Roberto Caronna
  • , Giovanni Casella
  • , Carlo Catalano
  • , Roberta Centello
  • , Enrico Cortesi
  • , Ferdinando D’Ambrosio
  • , Carlo Della Rocca
  • , Adriano De Santis
  • , Cira Rosaria Tiziana Di Gioia
  • , Valentina Di Vito
  • , Antongiulio Faggiano
  • , Tiziana Feola
  • , Daniele Gianfrilli
  • , Alfredo Genco
  • , Elisa Giannetta
  • , Franco Iafrate
  • , Andrea M. Isidori
  • , Andrea Lenzi
  • , Paolo Marchetti
  • , Francesca Maccioni
  • , Alessio Molfino
  • , Maurizio Muscaritoli
  • , Carla Pandozzi
  • , Giulia Puliani
  • , Franz Sesti
  • , Carola Severi
  • , Silverio Tomao
  • , Vincenzo Tombolini
  • , Federico Venuta
  •  & Monica Verrico

Corresponding author

Correspondence to Elisa Giannetta.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Ethics approval

The study has been approved by the review board of Sapienza University of Rome (reference number 5917).

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Puliani, G., Sesti, F., Anastasi, E. et al. Angiogenic factors as prognostic markers in neuroendocrine neoplasms. Endocrine 76, 208–217 (2022). https://doi.org/10.1007/s12020-021-02942-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-021-02942-4

Keywords

Search

Navigation