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.