Angioside: The role of Angiogenesis and Hypoxia in Lung Neuroendocrine Tumours According to Primary Tumour Location in Left or Right Parenchyma

Anna La Salvia, Raffaella Carletti, Monica Verrico, Tiziana Feola, Giulia Puliani, Massimiliano Bassi, Franz Sesti, Angelina Pernazza, Rossella Mazzilli, Giuseppe Lamberti, Alessandra Siciliani, Massimiliano Mancini, Chiara Manai, Federico Venuta, Mohsen Ibrahim, Silverio Tomao, Giulia D’Amati, Cira Di Gioia, Elisa Giannetta, Federico CappuzzoAntongiulio Faggiano

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Well-differentiated lung neuroendocrine tumours (Lu-NETs), classified as typical (TC) and atypical (AC) carcinoids, represent 30% of NETs. Angiogenesis plays an essential role in NET development and progression. A higher vascular network is a marker of differentiation, with positive prognostic implications. Materials and Methods: We retrospectively evaluated microvessel density (MVD) by CD34 immunohistochemical (IHC) staining and hypoxia by IHC staining for Hypoxia-inducible factor 1α (HIF-1α), comparing right- and left-lung parenchyma in 53 lung NETs. Results: The median age was 66 years (39–81), 56.6% males, 24.5% AC, 40.5% left-sided tumours and 69.8% TNM stage I. The mitotic count was <2/10 per 10 HPF in 79.2%, and the absence of necrosis in 81.1%, 39.6% with Ki67, was ≤2%. The MVD, the number of vessels and the average vessel area median values were significantly higher in the right than the left parenchyma (p: 0.025, p: 0.019, p: 0.016, respectively). Hypoxia resulted present in 14/19 (73.6%) left tumours and in 10/20 (50%) right tumours in the parenchyma (p: 0.129). Conclusions: This study suggests a biological rationale for a different angiogenesis and hypoxia according to the Lu-NETs’ location. In our study, left primary tumours were less vascularized and most likely to present hypoxia than right primary tumours. This finding could have potentially useful prognostic and predictive implications for Lu-NETs.

Original languageEnglish
Article number5958
JournalJournal of Clinical Medicine
Issue number19
StatePublished - Oct 2022


  • angiogenesis
  • hypoxia
  • left side
  • lung NET
  • necrosis
  • neuroendocrine tumours
  • prognostic factors


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