Chromogranin A: Is It a Useful Marker of Neuroendocrine Tumors?

Campana, Davide; Nori, Francesca; Piscitelli, L; Morselli-Labate, Antonio Maria; Pezzilli, Raffaele; Corinaldesi, Roberto; Tomassetti, Paola

doi:10.1200/jco.2006.10.1535

Cited by 213 publications

(155 citation statements)

References 26 publications

(31 reference statements)

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“…A number of putative tumour markers are measured in NET patients, with CgA having the highest expression in NETs and being considered the most useful diagnostic and prognostic marker (Janson et al, 1997;Turner et al, 2006;Campana et al, 2007). Tumour markers are measured at regular intervals and may be useful for monitoring disease progression.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, tumour markers can have prognostic value: plasma neurokinin-A has been shown to be an accurate marker of prognosis in midgut NETs, with rising neurokinin-A levels despite somatostatin analogue therapy shown to be associated with poorer prognosis (Turner et al, 2006); patients with CgA greater than 5000 mg l À1 have a 5-year survival of only 22% as opposed to 63% for patients with serum chromogranin-A levels of less than 5000 mg l À1 (Janson et al, 1997). Absolute plasma CgA levels may also help to differentiate between localised and diffuse NET spread, as well as between chronic active gastritis and NETs (Campana et al, 2007).…”

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confidence: 99%

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α-Fetoprotein and human chorionic gonadotrophin-β as prognostic markers in neuroendocrine tumour patients

et al. 2008

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Serum chromogranin A is the most useful general and prognostic tumour marker available for neuroendocrine tumour (NET) patients. The role of other tumour markers is less clear. In order to determine the diagnostic and prognostic value of serum afetoprotein (AFP) and human chorionic gonadotrophin-b (hCGb) in NETs, a database containing biochemical, histological, and survival data on 360 NET patients was constructed. This data was statistically assessed, using Statistical Package for the Social Sciences, to determine the utility of commonly measured tumour markers with particular emphasis on AFP and hCGb. a-Fetoprotein and hCGb were raised in 9.5 and 12.3% of patients respectively and jointly raised in 9.1% of patients in whom it was measured. aFetoprotein levels associated strongly and positively with tumour grade, serum CgA and hCGb levels, and worse survival. Human chorionic gonadotrophin-b levels also associated strongly and positively with serum CgA and AFP levels, and worsening survival. aFetoprotein and hCGb are elevated in high-grade NETs, with a rapidly progressive course and poorer survival. They also correlate with chromogranin-A, which is known to be a marker of tumour burden and to have prognostic value. Thus AFP and hCGb are clinically important in NETs and when elevated are poor prognostic markers.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

α-Fetoprotein and human chorionic gonadotrophin-β as prognostic markers in neuroendocrine tumour patients

et al. 2008

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“…A különböző endokrin szö-vetekben proteolitikus módosításokat követően alakul át extracellulárisan működő biológiailag aktív peptidformákká. A CgA-ból kialakuló fehérjék, mint a pancreastatin, a vasostatin, a WE-14 és további formák jelentős és specifi kus biológiai hatással rendelkeznek (1. táblázat) [26,27,28,29,30,34,35,45,47,48,49,50,51,52].…”

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The role of chromogranin-A and its derived peptide, WE-14 in the development of type 1 diabetes mellitus

et al. 2015

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A kromogranin-A a granincsaládba tartozó fehérje, amelyet neuroendokrin sejtek termelnek és ezek szekréciós granulumaiból származik. A kromogranin-A-ból számos, mind ez idáig kevésbé tisztázott funkciójú fehérje képződik. Jelenleg a kromogranin-A vérben mérhető szintjének meghatározását elsősorban neuroendokrin daganatok laboratóriumi diagnosztikájában használják. A legfrissebb kutatások alapján azonban úgy tűnik, a kromogranin-A-ból szár-mazó WE-14 nevű fehérjének szerepe lehet az 1-es típusú cukorbetegség kialakulásában is. A WE-14 fehérje autoantigénként viselkedik a β-sejtek elpusztításában részt vevő T-sejtek számára. Ezt a mechanizmust eddig specifi kusan a nem obes diabetogén egerekben fi gyelték meg. Újabb eredmények alapján a WE-14 a diabeteses egerek mellett az újonnan diagnosztizált 1-es típusú cukorbetegeknél is az autoreaktív sejtek célpontjaként szolgál, amely reakció szö-veti transzglutamináz enzimmel fokozható. A szerzők jelen összefoglalójukban áttekintik a kromogranin-A bioszintézisét, biokémiai jellegzetességeit, szervezetbeli funkcióit, valamint ismertetik a cukorbetegség patomechanizmusá-ban betöltött szerepére vonatkozó jelen ismereteket. Orv. Hetil., 2015, 156(5), 163-170. Kulcsszavak: kromogranin-A, diabetes mellitus, tumormarker, WE-14The role of chromogranin-A and its derived peptide, WE-14 in the development of type 1 diabetes mellitus Chromogranin-A is a member of the granine protein family. It is produced in neuroendocrine cells via secretory granules. Many cleavage proteins are formed from chromogranin-A, from which some have well known biological activity, while the function of others is not yet fully known. Serum chromogranin-A levels are used in neuroendocrine tumour diagnostics. Recent studies showed that one of its cleavage protein, WE-14 may also play a role in the development of type 1 diabetes. WE-14 may function as an autoantigen for T-cells involved in the destruction of β-cells. This mechanism was previously observed only in non-obese diabetic mice. Novel results show that WE-14 also serves as a target for autoreactive cells in newly diagnosed type 1 diabetic patients as well, which reaction can be increased with transglutaminase. In this paper the authors summarize the recent knowledge about chromogranin-A and its potential role in the pathomechanism of type 1 diabetes mellitus.Keywords: chromogranin-A, diabetes mellitus, tumour marker, Z., Nagy, P., Patócs, A., Somogyi, A. [The role of chromogranin-A and its derived peptide, WE-14 in the development of type 1 diabetes mellitus]. Orv. Hetil., 2015, 156(5), 163-170.

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“…Concentrations may be dependent on tumor features, such as: type, secretory activity, neuroendocrine differentiation degree and total burden (1,2). However, several lines of evidence show that the diagnostic accuracy is affected primarily by the type of assay used to measure CgA (1,(3)(4)(5). As a matter of fact, it has been reported that in healthy subjects, there is a discordance rate of ;20% between CgA concentrations measured using the two commercially available methods: immunoradiometric assay (IRMA) and enzyme-linked immunosorbent assay (ELISA) (1).…”

Section: Introductionmentioning

confidence: 99%

Impact of calibration fitting models on the clinical value of chromogranin A

Ferraro

Marano²,

Ciardi

et al. 2009

Clinical Chemistry and Laboratory Medicine

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Background: The clinical relevance of chromogranin A (CgA) concentrations depends on the analytical performance of the assay. The goal of the present study was to define the clinical involvements in CgA calibration models by evaluating the confidence intervals (CIs) for values from patients who were undergoing monitoring for disease. Methods: Thirty calibration curves for the CgA assay wimmunoradiometric assay (IRMA), (CIS-BIO)x were built using linear regression (LR), and four-parameter logistic models were used to estimate CIs for patient concentrations. Results: We reported the inadequacy of the LR curve estimation procedure. We showed: 1) no evidence that the straight calibration line could fit the average responses, 2) non-constant and non-uniform variance of the replicated calibration responses. All tests performed in the analysis of variance and CI calculation for the calibration curve should be invalidated. The four-parameter logistic function yielded results for 16 curves only; this result could be due to the low number and inappropriate concentration of calibrators. This suggests that some aspects of the assay design should be reviewed. However, using the variance function estimated in this model, we could assess the CI for calibration curves and patient samples. Conclusions: We showed that the four-parameter logistic calibration model with estimated variance function should better support clinical interpretation of marker concentration changes in patients serially tested.

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Chromogranin A: Is It a Useful Marker of Neuroendocrine Tumors?

Cited by 213 publications

References 26 publications

α-Fetoprotein and human chorionic gonadotrophin-β as prognostic markers in neuroendocrine tumour patients

α-Fetoprotein and human chorionic gonadotrophin-β as prognostic markers in neuroendocrine tumour patients

The role of chromogranin-A and its derived peptide, WE-14 in the development of type 1 diabetes mellitus

Impact of calibration fitting models on the clinical value of chromogranin A

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