Owing to the heterogeneity of neuroendocrine neoplasms (NENs), the availability of reliable circulating markers is critical for improving diagnostics, prognostic stratification, follow-up, and definition of treatment strategy. This review is focused on Chromogranin A (CgA), a hydrophilic glycoprotein present in large dense core vesicles of neuroendocrine cells. Despite being long identified as the most useful NEN-related circulating marker, clinical application of CgA is controversial. CgA assays still lack of standardization, thus hampering not only clinical management but also the comparison between different analyses. In the diagnostic setting, clinical utility of CgA is limited as hampered by a) the variety of oncological and non-oncological conditions affecting marker levels, which impairs specificity; b) the fact that 30-50% of NENs show normal CgA, which impairs sensitivity. Regarding the prognostic phase, there is prospective evidence which demonstrates that advanced NENs secreting CgA have poorer outcome, as compared with those showing non-elevated marker levels. Although the identification of cut-offs allowing a proper risk stratification of CgA secreting patients has not been performed, this represents the most important clinical application of the marker. By contrast, based on prospective studies, the trend of elevated circulating CgA does not represent a valid indicator of morphological evolution and has therefore no utility for the follow-up phase. Ultimately, current knowledge about the role of the marker for the definition of treatment strategy is poor and is limited by the small number of available studies, their prevalent retrospective nature and the absence of control groups of untreated subjects.

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame

Zatelli MC
Co-primo
;
Ambrosio MR;Bondanelli M;
2018

Abstract

Owing to the heterogeneity of neuroendocrine neoplasms (NENs), the availability of reliable circulating markers is critical for improving diagnostics, prognostic stratification, follow-up, and definition of treatment strategy. This review is focused on Chromogranin A (CgA), a hydrophilic glycoprotein present in large dense core vesicles of neuroendocrine cells. Despite being long identified as the most useful NEN-related circulating marker, clinical application of CgA is controversial. CgA assays still lack of standardization, thus hampering not only clinical management but also the comparison between different analyses. In the diagnostic setting, clinical utility of CgA is limited as hampered by a) the variety of oncological and non-oncological conditions affecting marker levels, which impairs specificity; b) the fact that 30-50% of NENs show normal CgA, which impairs sensitivity. Regarding the prognostic phase, there is prospective evidence which demonstrates that advanced NENs secreting CgA have poorer outcome, as compared with those showing non-elevated marker levels. Although the identification of cut-offs allowing a proper risk stratification of CgA secreting patients has not been performed, this represents the most important clinical application of the marker. By contrast, based on prospective studies, the trend of elevated circulating CgA does not represent a valid indicator of morphological evolution and has therefore no utility for the follow-up phase. Ultimately, current knowledge about the role of the marker for the definition of treatment strategy is poor and is limited by the small number of available studies, their prevalent retrospective nature and the absence of control groups of untreated subjects.
Marotta, V; Zatelli, Mc; Sciammarella, C; Ambrosio, Mr; Bondanelli, M; Colao, A; Faggiano, A.
File in questo prodotto:
File Dimensione Formato  
R11.full (chromogranin 2018).pdf

solo gestori archivio

Descrizione: Full text editoriale
Tipologia: Full text (versione editoriale)
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 547.7 kB
Formato Adobe PDF
547.7 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
2378768 Bondanelli pre-print.pdf

accesso aperto

Descrizione: pre print
Tipologia: Pre-print
Licenza: PUBBLICO - Pubblico con Copyright
Dimensione 505.46 kB
Formato Adobe PDF
505.46 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11392/2378768
Citazioni
  • ???jsp.display-item.citation.pmc??? 36
  • Scopus 75
  • ???jsp.display-item.citation.isi??? 78
social impact