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Expression of ghrelin is correlated to good outcome in invasive breast cancer
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 Oncology, Radiology and Clinical Immunology.
Institutionen för laboratoriemedicin, Avd för Patologi, Malmö Universitetssjukhus.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Onkologisk endokrinologi)
(English)Manuscript (preprint) (Other (popular science, discussion, etc.))
Abstract [en]

Purpose: Expression of the peptide hormones ghrelin and obestatin has previously been demonstrated in human mammary glands. However, the clinical implications of the expression of these peptides in breast cancer are unclear. The aim of this study was to investigate the potential clinical value of ghrelin and obestatin as breast cancer biomarkers.

Experimental Design: A tissue microarray containing breast cancer specimens from 144 patients was immunostained with antibodies versus ghrelin and obestatin. The expression of the two peptides was evaluated and correlated to previously known prognostic factors in breast cancer and to the outcome. Cox-regression analysis was used to assess whether these markers may predict survival status of breast cancer patients.

Results: Moderate to strong immunoreactivity for ghrelin and obestatin was observed in 71.5% and 77.1% of the cases, respectively. Ghrelin and obestatin expression was significantly but weakly correlated to low histological grade, estrogen receptor positivity, small tumor size and low proliferation. In both uni- and multivariate analyses ghrelin expression was correlated to significantly better recurrence-free and breast cancer-specific survival. Reproducibility between the two readers was very good for both stainings with kappa values of 0.94-1.00.

Conclusion: Patients with tumors expressing ghrelin had 2-3 times lower risk for recurrence or breast cancer death than those lacking ghrelin expression. Ghrelin expression is easily assessable with high reproducibility using immunohistochemistry. Further investigations are needed to establish the clinical significance of ghrelin as a biomarker in breast cancer.

Keyword [en]
breast cancer, ghrelin, mammary gland, obestatin
National Category
Medical and Health Sciences
Research subject
Endocrinology and Diabetology
Identifiers
URN: urn:nbn:se:uu:diva-129500OAI: oai:DiVA.org:uu-129500DiVA: diva2:354739
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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