Ricerc@Sapienza

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 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.