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Expression of ghrelin and obestatin in neuroendocrine tumors
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Onkologisk endokrinologi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Introduction: The peptide hormones ghrelin and obestatin are derived from the same hormone precursor. Ghrelin, which is mainly produced by the gastric mucosa, is involved in many biological processes ranging from growth hormone release to appetite regulation. Obestatin has an identical distribution as ghrelin but its physiological function still needs further investigation. The aim of the present study was to elucidate the incidence of ghrelin- and obestatin-immunoreactive cells in a comprehensive panel of human neuroendocrine tumors (NETs).

Material and Methods: Immunohistochemistry with polyclonal antibodies vs. ghrelin and obestatin was used to investigate the expression of the two peptides in NETs (n=128) and other endocrine-related disorders (n=3). Co-expression of the peptides was evaluated by double-immunofluorescence.

Results: Ghrelin and obestatin were expressed in 13/128 and 14/128 tumor tissues respectively, mainly representing NETs of foregut and less of hindgut origin. Double immunofluorescence staining showed co-localization of the peptides. Ghrelin and obestatin were also detected in pancreatic tissue from a nesiodioblastosis patient.

Conclusion: A minority of NETs, mainly of foregut origin, express ghrelin and obestatin. Our results indicate that these hormones should not be included in the general work-up of patients with NETs. The significance of the few ghrelin and obestatin immunoreactive tumor cells has to be further explored.

Keyword [en]
obestatin, ghrelin, neuroendocrine tumors, immunohistochemistry
National Category
Medical and Health Sciences
Research subject
Endocrinology and Diabetology
Identifiers
URN: urn:nbn:se:uu:diva-129501OAI: oai:DiVA.org:uu-129501DiVA: diva2:354735
Projects
Expression of neuroendocrine markers in normal and neoplastic tissue with an emphasis on ghrelin and obestatin
Available from: 2010-10-04 Created: 2010-08-17 Last updated: 2011-11-08
In thesis
1. Expression of Neuroendocrine Markers in Normal and Neoplastic Tissue with an Emphasis on Ghrelin and Obestatin
Open this publication in new window or tab >>Expression of Neuroendocrine Markers in Normal and Neoplastic Tissue with an Emphasis on Ghrelin and Obestatin
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis was to characterize the expression of the peptides ghrelin and obestatin, as well as other neuroendocrine markers in human normal tissues, in invasive breast cancer and a wide panel of neuroendocrine tumors (NETs).

In normal tissues the expression of ghrelin and obestatin was mainly localized to the gastric mucosa, and in lesser extent in the remaining gastrointestinal tract, endocrine pancreas and mammary glands. Double immunofluorescence studies demonstrated that ghrelin and obestatin were co-localized in the same cells displaying the same cytoplasmic distribution.

In normal breast tissue, ghrelin, obestatin, adrenomedullin, apelin and vesicular monoamine transporter 2 were specifically demonstrated in the luminal epithelial cells. Consecutive sections indicated that mammary epithelial cells could express several of these peptides. Secretogranin II and III were also detected in breast tissue, but their presence was restricted to the outer layer of myoepithelial cells, whereas chromogranin B immunoreactivity was found in both the epithelial and myoepithelial cells.

Ghrelin and obestatin immunoreactivity was seen in invasive breast cancer, where the expression could be correlated to factors associated with prognosis. Furthermore, multivariate analysis indicated that ghrelin expression was a possible independent prognostic factor for prolonged recurrence-free and breast cancer-specific survival.

In a panel of NETs and endocrine-related disorders it was revealed that ghrelin and obestatin immunoreactivity was primarily found in tumors originating from the respective normal tissues. The two proteins were detected in only a few cases and only occasional tumor cells were immunoreactive.

In conclusion, ghrelin and obestatin are localized in the gastrointestinal tract, endocrine pancreas and mammary glands. This thesis has contributed to our understanding of the distribution of ghrelin and obestatin in both normal tissue and tumor cells. A potential role of ghrelin as a prognostic factor in invasive breast cancer has been identified and should be further explored.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 64 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 604
Keyword
ghrelin, obestatin, neuroendocrine marker, immunohistochemistry, neuroendocrine tumors, breast cancer, mammary glands
National Category
Medical and Health Sciences
Research subject
Endocrinology and Diabetology
Identifiers
urn:nbn:se:uu:diva-130972 (URN)978-91-554-7909-1 (ISBN)
Public defence
2010-11-20, Enghoffsalen, Ingång 50, Akademiska sjukhuset, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2010-10-28 Created: 2010-09-20 Last updated: 2011-01-13Bibliographically approved

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