Chromogranin a Measurement in Metastatic Well-Differentiated Gastroenteropancreatic Neuroendocrine Carcinoma: Screening for False Positives and a Prospective Follow-Up Study
Free accessResearch articleFirst published online April, 2011
Chromogranin a Measurement in Metastatic Well-Differentiated Gastroenteropancreatic Neuroendocrine Carcinoma: Screening for False Positives and a Prospective Follow-Up Study
Multiple causes of false-positive chromogranin A (CgA) measurement have been reported that may affect its impact as a surrogate marker of RECIST progression in well-differentiated gastroenteropancreatic neuroendocrine tumors (WDGEPNET).
Aims
1) To evaluate the frequency of false-positive CgA results. 2) To prospectively compare CgA variations with RECIST morphological changes in patients without known causes of false-positive CgA measurements.
Methods
First, the conditions responsible for potentially false-positive CgA measurements were screened in 184 consecutive patients with metastatic WDGEPNET. Secondly, a variation in CgA at a 6-month interval was compared to RECIST results at 6 months in 46 patients.
Results
Among 184 patients, elevated CgA was found in 130 cases (71%) including 99 patients with at least one cause of a false-positive result. Impaired kidney function as well as medication with proton pump inhibitors were found to be the 2 major causes of false-positive results. The sensitivity and specificity of CgA measurements compared with morphological tumor changes according to the RECIST criteria were 71% and 50%, respectively, at 6 months.
Conclusion
Routine screening for the causes of false-positive CgA measurements is mandatory in WDGEPNET patients. Our study does not validate the use of CgA as a surrogate marker of tumor progression.
O'TooleD., GrossmanA., GrossD.ENETS consensus guidelines for the standards of care in neuroendocrine tumors: biochemical markers.Neuroendocrinology2009; 90: 194–202.
2.
BaudinE., BidartJ.M., BachelotA.Impact of chromogranin A measurement in the work-up of neuroendocrine tumors.Ann Oncol2001; 12(Suppl 2): S79–82.
3.
BaudinE., GigliottiA., DucreuxM.Neuron-specific enolase and chromogranin A as markers of neuroendocrine tumours.Br J Cancer1998; 78: 1102–7.
4.
HsiaoR.J., ParmerR.J., TakiyyuddinM.A., O'ConnorD.T.Chromogranin A storage and secretion: sensitivity and specificity for the diagnosis of pheochromocytoma.Medicine (Baltimore)1991; 70: 33–45.
5.
CampanaD., NoriF., PiscitelliL.Chromogranin A: is it a useful marker of neuroendocrine tumors?J Clin Oncol2007; 25: 1967–73.
6.
NobelsF.R., KwekkeboomD.J., CoopmansW.Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones.J Clin Endocrinol Metab1997; 82: 2622–8.
7.
TomassettiP., MiglioriM., SimoniP.Diagnostic value of plasma chromogranin A in neuroendocrine tumours.Eur J Gastroenterol Hepatol2001; 13: 55–8.
8.
SeregniE., FerrariL., BajettaE., MartinettiA., BombardieriE.Clinical significance of blood chromogranin A measurement in neuroendocrine tumours.Ann Oncol2001; 12(Suppl 2): S69–72.
9.
ZatelliM.C., TortaM., LeonA.Chromogranin A as a marker of neuroendocrine neoplasia: an Italian multicenter study.Endocr Relat Cancer2007; 14: 473–82.
10.
LeonA., TortaM., DittadiR.Comparison between two methods in the determination of circulating chromogranin A in neuroendocrine tumors (NETs): results of a prospective multicenter observational study.Int J Biol Markers2005; 20: 156–68.
11.
GiustiM., SidotiM., AugeriC., RabittiC., MinutoF.Effect of short-term treatment with low dosages of the proton-pump inhibitor omeprazole on serum chromogranin A levels in man.Eur J Endocrinol2004; 150: 299–303.
12.
SyversenU., MignonM., BonfilsS., KristensenA., WaldumH.L.Chromogranin A and pancreastatin-like immunoreactivity in serum of gastrinoma patients.Acta Oncol1993; 32: 161–5.
13.
HsiaoR.J., MezgerM.S., O'ConnorD.T.Chromogranin A in uremia: progressive retention of immunoreactive fragments.Kidney Int1990; 37: 955–64.
14.
PieroniM., CortiA., TotaB.Myocardial production of chromogranin A in human heart: a new regulatory peptide of cardiac function.Eur Heart J2007; 28: 1117–27.
15.
NobelsF.R., de HerderW.W., KwekkeboomD.J.Serum chromogranin A in the differential diagnosis of Cushing's syndrome.Eur J Endocrinol1994; 131: 589–93.
16.
SciolaV., MassironiS., ConteD.Plasma chromogranin a in patients with inflammatory bowel disease.Inflamm Bowel Dis2009; 15: 867–71.
17.
Al-ShoumerK.A., VasanthyB.A.Serum chromogranin A concentration in hyperthyroidism before and after medical treatment.J Clin Endocrinol Metab2009; 94: 2321–4.
18.
BerrutiA., DogliottiL., MoscaA.Potential clinical value of circulating chromogranin A in patients with prostate carcinoma.Ann Oncol2001; 12(Suppl 2): S153–7.
19.
GranbergD., StridsbergM., SeensaluR.Plasma chromogranin A in patients with multiple endocrine neoplasia type 1.J Clin Endocrinol Metab1999; 84: 2712–7.
20.
BajettaE., FerrariL., MartinettiA.Chromogranin A, neuron specific enolase, carcinoembryonic antigen, and hydroxyindole acetic acid evaluation in patients with neuroendocrine tumors.Cancer1999; 86: 858–65.
21.
Abou-SaifA., GibrilF., OjeaburuJ.V.Prospective study of the ability of serial measurements of serum chromogranin A and gastrin to detect changes in tumor burden in patients with gastrinomas.Cancer2003; 98: 249–61.
22.
NeharD., Lombard-BohasC., OlivieriS.Interest of chromogranin A for diagnosis and follow-up of endocrine tumours.Clin Endocrinol (Oxf)2004; 60: 644–52.
23.
NikouG.C., MarinouK., ThomakosP.Chromogranin a levels in diagnosis, treatment and follow-up of 42 patients with non-functioning pancreatic endocrine tumours.Pancreatology2008; 8: 510–9.
24.
ArnoldR., WilkeA., RinkeA.Plasma chromogranin A as marker for survival in patients with metastatic endocrine gastroenteropancreatic tumors.Clin Gastroenterol Hepatol2008; 6: 820–7.
25.
EkebladS., SkogseidB., DunderK., ObergK., ErikssonB.Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution.Clin Cancer Res2008; 14: 7798–803.
26.
YaoJ.C., Lombard-BohasC., BaudinE.Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial.J Clin Oncol2010; 28: 69–76.
27.
WelinS., StridsbergM., CunninghamJ.Elevated plasma chromogranin A is the first indication of recurrence in radically operated midgut carcinoid tumors.Neuroendocrinology2009; 89: 302–7.
28.
SolciaE., KlöppelG., and SobinL.Histological typing of endocrine tumours.WHO international histological classification of tumours.Berlin: Springer, 2000.
29.
RindiG., KloppelG., CouvelardA.TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system.Virchows Archiv2007; 451: 757–62.
MarieI., MoutotA., TharrasseA.Validity of proton pump inhibitors' prescriptions in a department of internal medicine.Rev Med Interne2007; 28: 86–93.
32.
StridsbergM., ErikssonB., FellstromB., KristianssonG., Tiensuu JansonE.Measurements of chromogranin B can serve as a complement to chromogranin A.Regul Pept2007; 139: 80–3.
33.
SundinA., VulliermeM.P., KaltsasG., PlockingerU.ENETS consensus guidelines for the standards of care in neuroendocrine tumors: radiological examinations.Neuroendocrinology2009; 90: 167–83.
34.
StridsbergM., ErikssonB., ObergK., JansonE.T.A comparison between three commercial kits for chromogranin A measurements.J Endocrinol2003; 177: 337–41.
35.
VerderioP., DittadiR., MarubiniE.An Italian program of external quality control for chromogranin A (CgA) assay: performance evaluation of CgA determination.Clin Chem Lab Med2007; 45: 1244–50.
36.
StivanelloM., BerrutiA., TortaM.Circulating chromogranin A in the assessment of patients with neuroendocrine tumours. A single institution experience.Ann Oncol2001; 12(Suppl 2): S73–7.
