Major hyperghrelinemia in advanced well-differentiated neuroendocrine carcinomas: report of three cases

Walter, Thomas; Chardon, Laurence; Hervieu, Valérie; Cohen, R. S.; Chayvialle, J.A.; Scoazec, Jean Yves; Lombard‐Bohas, Catherine

doi:10.1530/eje-09-0073

Cited by 21 publications

(13 citation statements)

References 30 publications

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“…NETs can also express ghrelin and its receptors (14, 22). Although most NETs release ghrelin, hyperghrelinemia has been reported in only 11 patients with NETs (23, 24, 25, 26, 27). …”

Section: Introductionmentioning

confidence: 99%

Plasma acylated and plasma unacylated ghrelin: useful new biomarkers in patients with neuroendocrine tumors?

Adrichem

Lely

Huisman

et al. 2016

Endocrine Connections

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To date, the value of fasting plasma acylated ghrelin (AG) and unacylated ghrelin (UAG) as potential novel biomarkers in patients with neuroendocrine tumors (NETs) is unknown. The aims of this study are to (i) compare fasting AG and UAG levels between nonobese, nondiabetic NET patients (N=28) and age- (±3 years) and sex-matched nonobese, nondiabetic controls (N=28); and (ii) study the relationship between AG, UAG, and AG/UAG ratios and biochemical (chromogranin-A (CgA) and neuron-specific enolase (NSE) levels) and clinical parameters (age at diagnosis, sex, primary tumor location, carcinoid syndrome, ENETS TNM classification, Ki-67 proliferation index, grading, prior incomplete surgery) in NET patients. Fasting venous blood samples (N=56) were collected and directly stabilized with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride after withdrawal. Plasma AG and UAG levels were determined by ELISA. Expression of ghrelin was examined in tumor tissue by immunohistochemistry. There were no significant differences between NET patients and controls in AG (median: 62.5 pg/mL, IQR: 33.1–112.8 vs median: 57.2pg/mL, IQR: 26.7–128.3, P=0.66) and UAG in levels (median: 76.6pg/mL, IQR: 35.23–121.7 vs median: 64.9, IQR: 27.5–93.1, P=0.44). No significant correlations were found between AG, UAG, and AG/UAG ratios versus biochemical and clinical parameters in NET patients with the exception of age at diagnosis (AG: ρ= −0.47, P=0.012; AG/UAG ratio: ρ= −0.50, P=0.007) and baseline chromogranin-A levels (AG/UAG ratio: ρ= −0.44, P=0.019). In our view, fasting plasma acylated and unacylated ghrelin appear to have no value as diagnostic biomarkers in the clinical follow-up of patients with NETs.

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“…NETs can also express ghrelin and its receptors (14, 22). Although most NETs release ghrelin, hyperghrelinemia has been reported in only 11 patients with NETs (23, 24, 25, 26, 27). …”

Section: Introductionmentioning

confidence: 99%

Plasma acylated and plasma unacylated ghrelin: useful new biomarkers in patients with neuroendocrine tumors?

Adrichem

Lely

Huisman

et al. 2016

Endocrine Connections

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“…Serum levels of active ghrelin were significantly higher in patients with prostate (18), ovarian (10), and hepatocellular carcinoma (11). Major hyperghrelinemia was observed in end-stage well-differentiated neuroendocrine carcinomas (25). Corbetta and cols.…”

Section: Resultsmentioning

confidence: 99%

Serum ghrelin levels in papillary thyroid carcinoma

Uçan

Şahi̇n

Kızılgül

et al. 2017

Arch. Endocrinol. Metab.

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Objective: Ghrelin plays a role in several processes of cancer progression, and numerous cancer types express ghrelin and its receptor. We aimed to investigate serum levels of ghrelin in patients with papillary thyroid carcinoma (PTC) and its association with the prognostic factors in PTC. Materials and methods: We enrolled 54 patients with thyroid cancer (7 male, 47 female) and 24 healthy controls (6 male, 18 female) in the study. We compared demographic, anthropometric, and biochemical data, and serum ghrelin levels between the groups. Serum ghrelin levels were measured using as enzyme-linked immunosorbent assay. Results: Ghrelin levels were similar between the groups, but plasma ghrelin levels were significantly higher in tumors larger than 1 cm diameter compared with papillary microcarcinomas. Serum ghrelin levels also correlated with tumor size (r = 0.499; p < 0.001). Body mass index, thyroid-stimulating hormone, and HOMA-IR levels were similar between the groups. There were no statistically significant differences regarding average age and other prognostic parameters including lymph node invasion, capsule invasion, multifocality and surgical border invasion between patients with microcarcinoma and tumors larger than 1 cm. Conclusion: In our study, no significant difference in serum ghrelin levels was determined between patients with papillary thyroid cancer and healthy controls however, serum ghrelin levels were higher in tumors larger than 1 cm compared to in those with thyroid papillary microcarcinoma. Arch Endocrinol Metab. 2017;61(5):464-9

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“…Furthermore, NETs originating from the gastric mucosa, pancreas, gallbladder and rectum, displaying ghrelin-IR tumor cells, have been shown to secrete ghrelin causing hyperghrelinemia [18,19,20]. In addition, ghrelin-IR cells have been identified in various hyperplasia patterns, in foci of neuroendocrine cell hyperplasia localized in the mucosa adjacent to gastric NETs, but in these cases, circulating ghrelin levels remained normal [17,21,22].…”

Section: Introductionmentioning

confidence: 99%

Ghrelin and Obestatin in Human Neuroendocrine Tumors: Expression and Effect on Obestatin Levels after Food Intake

Grönberg¹,

Tsolakis²,

Holmbäck³

et al. 2012

Neuroendocrinology

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Background: Ghrelin and obestatin are derived from the same peptide hormone precursor and are mainly produced by the gastric mucosa. Ghrelin is involved in many biological processes, whereas the physiological function of obestatin needs further investigation. The aims of the present study were to establish the incidence of ghrelin- and obestatin-immunoreactive cells in a comprehensive panel of human neuroendocrine tumors (NETs) and to investigate if blood obestatin concentrations are influenced during a standardized meal stimulation test in healthy individuals and patients with NETs. Materials and Methods: The expression of ghrelin and obestatin was investigated in NETs (n = 149) and other endocrine-related disorders (n = 3) using immunohistochemistry with specific polyclonal antibodies. Coexpression of the peptides was evaluated by double immunofluorescence. Concentrations of obestatin in blood were measured during a meal test in 6 healthy individuals and 5 patients with pancreatic NETs. Results: Ghrelin and obestatin were expressed in 14/152 and 19/152 tumor tissues, respectively, mainly representing NETs of foregut origin and in pancreatic tissue from a nesidioblastosis patient. Double immunofluorescence staining showed colocalization of the peptides. During the meal test, obestatin levels in blood were unchanged in all patients but decreased significantly in the healthy individuals. Conclusion: Only a minority of NETs express ghrelin and obestatin. However, analysis of patients with tumors originating from tissues that express the peptides in normal conditions could be of importance. The results from the meal test indicate that the hormone levels are affected by food intake in healthy individuals, whereas obestatin levels remained unchanged in pancreatic NET patients.

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Major hyperghrelinemia in advanced well-differentiated neuroendocrine carcinomas: report of three cases

Cited by 21 publications

References 30 publications

Plasma acylated and plasma unacylated ghrelin: useful new biomarkers in patients with neuroendocrine tumors?

Plasma acylated and plasma unacylated ghrelin: useful new biomarkers in patients with neuroendocrine tumors?

Serum ghrelin levels in papillary thyroid carcinoma

Ghrelin and Obestatin in Human Neuroendocrine Tumors: Expression and Effect on Obestatin Levels after Food Intake

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