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.
Keywords: myometrium; leiomyoma; leiomyosarcoma; phosphorylation; EGFR; tyrosine kinase
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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.
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. International Journal of Molecular Sciences. 2013; 14(3):4783-4792.
Weissenbacher, Tobias; Vrekoussis, Thomas; Roeder, David; Makrigiannakis, Antonis; Mayr, Doris; Ditsch, Nina; Friese, Klaus; Jeschke, Udo; Dian, Darius. 2013. "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. 14, no. 3: 4783-4792.