Does somatostatin or gastric inhibitory peptide receptor expression correlate with tumor grade and stage in gut neuroendocrine tumors?

Körner Jachertz, Meike; Waser, Beatrice; Reubi, Jean Claude (2015). Does somatostatin or gastric inhibitory peptide receptor expression correlate with tumor grade and stage in gut neuroendocrine tumors? Neuroendocrinology, 101(1), pp. 45-57. Karger 10.1159/000371804

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BACKGROUND/AIMS Important characteristics of neuroendocrine neoplasms (NEN) for prognosis and therapeutic decisions are the MIB-1 proliferative index (tumor grade) and tumor stage. Moreover, these tumors express peptide hormone receptors like somatostatin and gastric inhibitory peptide (GIP) receptors which represent important established and potential future targets, respectively, for molecular imaging and radiotherapy. However, the interrelation between tumor proliferation, stage, and peptide receptor amounts has never been assessed. METHODS In 114 gastrointestinal and bronchopulmonary NEN, the proliferative rate assessed with MIB-1 immunohistochemistry and tumor stage were compared with the somatostatin type 2 receptor (sst2) and GIP receptor expression measured quantitatively with in vitro receptor autoradiography. RESULTS NEN generally showed high sst2 and GIP receptor expression. GIP receptor but not sst2 expression correlated with the MIB-1 index. GIP receptor levels gradually increased in a subset of insulinomas and nonfunctioning pancreatic NEN, and decreased in ileal and bronchopulmonary NEN with increasing MIB-1 rate. MIB-1 levels were identified, above which GIP receptor levels were consistently high or low. These MIB-1 levels were clearly different from those defining tumor grade. In grade 3 NEN, GIP receptor levels were always low, while sst2 levels were variable and sometimes extremely high. Conversely, sst2 expression correlated more frequently with tumor stage than GIP receptor expression, with metastasized NEN showing higher sst2 levels than localized tumors. CONCLUSIONS sst2, a clinically crucial molecular target, shows variable and unpredictable expression in NEN irrespective of tumor grade. Therefore, each NEN should be tested for sst2 if clinical applications with somatostatin analogs are considered. Conversely, the potential future role of GIP receptors as molecular targets in NEN may be dependent on the MIB-1 level.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Körner Jachertz, Meike; Waser, Beatrice and Reubi-Kattenbusch, Jean-Claude

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0028-3835

Publisher:

Karger

Language:

English

Submitter:

Doris Haefelin

Date Deposited:

13 Jul 2015 09:55

Last Modified:

17 Oct 2019 11:12

Publisher DOI:

10.1159/000371804

PubMed ID:

25591947

BORIS DOI:

10.7892/boris.70213

URI:

https://boris.unibe.ch/id/eprint/70213

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