Int. J. Mol. Sci. 2013, 14(3), 4783-4792; doi:10.3390/ijms14034783
Analysis of Epithelial Growth Factor-Receptor (EGFR) Phosphorylation in Uterine Smooth Muscle Tumors: Correlation to Mucin-1 and Galectin-3 Expression
Tobias Weissenbacher 1, Thomas Vrekoussis 1, David Roeder 1, Antonis Makrigiannakis 2, Doris Mayr 3, Nina Ditsch 4, Klaus Friese 1,4, Udo Jeschke 1,†,*
and Darius Dian 1,†
and Darius Dian 1,†1
Department of Obstetrics and Gynaecology, Innenstadt Campus, Ludwig-Maximilians-University, Munich 80337, Germany
2
Department of Obstetrics and Gynaecology & Laboratory of Human Reproduction, Medical School, University of Crete, Iraklion 71110, Greece
3
Department of Pathology, Ludwig-Maximilians-University, Munich 80337, Germany
4
Department of Obstetrics and Gynaecology, Grosshadern Campus, Ludwig-Maximilians-University, Munich 81377, Germany
†
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 8 January 2013 / Revised: 8 February 2013 / Accepted: 19 February 2013 / Published: 28 February 2013
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Abstract
Uterine fibroids are the commonest uterine benign tumors. A potential mechanism of malignant transformation from leiomyomas to leiomyosarcomas has been described. Tyrosine phosphorylation is a key mechanism that controls biological functions, such as proliferation and cell differentiation. The aim of the current study was to evaluate the phosphorylation of epithelial growth factor-receptor (EGFR) in normal myometrium, uterine myomas and uterine leiomyosarcomas. Formalin-fixed paraffin-embedded tissue samples from normal myometrium, leiomyomas and leiomyosarcomas were studied. Samples were immunohistochemically (IHC) assessed using the anti-EGFR phosphorylation of Y845 (pEGFR-Y845) and anti-pEGFR-Y1173 phosphorylation-specific antibodies. IHC staining was evaluated using a semiquantitative score. The expression of pEGFR-Y845 was significantly upregulated in leiomyosarcomas (p < 0.001) compared to leiomyomas and normal myometrium. In contrast, pEGFR-Y1173 did not differ significantly between the three groups of the study. Correlation analysis revealed an overall positive correlation between pEGFR Y845 and mucin 1 (MUC1). Further subgroup analysis within the tumoral group (myomas and leiomyosarcomas) revealed an additional negative correlation between pEGFR Y845 and galectin-3 (gal-3) staining. On the contrary no significant correlation was noted within the non-tumoral group. An upregulated EGFR phosphorylation of Y845 in leiomyosarcomas compared to leiomyomas implicates EGFR activation at this special receptor site. Due to these pEGFR-Y845 variations, it can be postulated that MUC1 interacts with it, whereas gal-3 seems to be cleaved from Y845 phosphorylated EGFR. Further research on this field could focus on differences in EGFR pathways as a potentially advantageous diagnostic tool for investigation of benign and malignant signal transduction processes. View Full-TextKeywords:
myometrium; leiomyoma; leiomyosarcoma; phosphorylation; EGFR; tyrosine kinase
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Weissenbacher, T.; Vrekoussis, T.; Roeder, D.; Makrigiannakis, A.; Mayr, D.; Ditsch, N.; Friese, K.; Jeschke, U.; Dian, D. Analysis of Epithelial Growth Factor-Receptor (EGFR) Phosphorylation in Uterine Smooth Muscle Tumors: Correlation to Mucin-1 and Galectin-3 Expression. Int. J. Mol. Sci. 2013, 14, 4783-4792.
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