Analysis of Epithelial Growth Factor-Receptor (EGFR) Phosphorylation in Uterine Smooth Muscle Tumors

Uterine fibroids are the commonest uterine benign tumors. A
potential mechanism of malignant transformation from leiomyomas to
leiomyosarcomas has beendescribed. 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.