Chromogranin-A as a serum marker for neuroendocrine tumors: comparison with neuron-specific enolase and correlation with immunohistochemical findings.
BACKGROUND
Chromogranin-A (Cg-A) is a 439-amino-acid protein contained in secretory granules of neuroendocrine cells, in addition to specific hormone peptides or neuropeptides. Since Cg-A is co-released with peptide hormones its serum concentration can be used as a marker of neuroendocrine tumors.


OBJECTIVE
Evaluation of the analytical performance of a new IRMA method for Cg-A assay and of the clinical value of serum Cg-A and neuron-specific enolase (NSE) in neuroendocrine tumors. In addition, we compared the diagnostic usefulness of both Cg-A and NSE serum levels and their relationship to tissue expression.


METHODS
Initially we evaluated the analytical performance (intra- and interassay imprecision, dilution test and detection limit) of the Cg-A RIACT method (CIS Bio-International, Gif-sur-Yvette, France). We selected 50 patients affected by various histologically confirmed neuroendocrine tumors (NETs): 111In-pentetreotide scan and helical computed tomography were employed to assess tumor extent. Cg-A and NSE were measured before surgery in serum samples of patients and 50 age-matched controls by IRMA methods. After surgery immunohistochemical stains for Cg-A and NSE were performed on surgical specimens of tumor tissue.


RESULTS
Cg-A levels were significantly higher (p < 0.0001) in patients with NETs than in healthy controls and we found a positive correlation between serum and tissue expression (p < 0.05). Serum levels of Cg-A were also related to tumor extent (p < 0.05) but in some cases we observed significant elevation of serum Cg-A in small, intensely immunoreactive NETs. ROC curve analysis showed better accuracy for serum Cg-A compared to NSE in the diagnosis of NETs, while no significant relationship was found between serum expression and immunostaining for NSE.


CONCLUSIONS
Our results confirmed the biological and clinical significance of circulating Cg-A as an expression of granular content in neuroendocrine tissues and supported the complementary usefulness of serum Cg-A in the diagnosis and evaluation of NETs together with imaging modalities.
Giovanella
L
L
Department of Nuclear Medicine, University Hospital Ospedale di Circolo e Fondazione Macchi, Varese, Italy.
La Rosa
S
S
Ceriani
L
L
Uccella
S
S
Erba
P
P
Garancini
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D053379:Chromogranin A; D002864:Chromogranins / Q000097:blood*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000175:diagnosis*; D010751:Phosphopyruvate Hydratase / Q000097:blood*
D014408:Biomarkers, Tumor; C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D010751:Phosphopyruvate Hydratase