Introduction:
The alterations of EGFR and
HER2/neu
as growth factor receptors and the cytoplasmic signal transduction proteins of RAS/RAF/MAP kinases including its end effector molecule (
ERK
) are important in the carcinogenesis of many tumors. The activation of these protooncogenes in prostate cancer is still under investigation. The aim of this work was to study
EGFR
, HER2- neu, inactive (non-phosphorylated) and active (phosphorylated)
ERK
expression in prostatic adenocarcinomas in correlation to the clinical and pathological parameters.
Methods:
Immunohistochemistry- using tissue microarrays- for
EGFR
,
HER2/neu
, non-phosphorylated, and phosphor-
ERK
, was performed on tissues from 166 patients- with primary prostatic adenocarcinoma with no prior treatment-. The results of different markers expression were correlated with the clinical and pathological parameters and were analyzed statistically.
Results:
The prostatic tissue showed
EGFR
, HER2 neu, phosphorylated and non-phosphorylated
ERK
expression in 8.4%, 1.4%, 78.2%, and 83.4% respectively whether low (patchy) or high expression (diffuse). There were no significant correlations found between patient characteristics and expression of the tested markers. The negative immune reactivity for non-phosphorylated
ERK
and
EGFR
- was significantly correlated with high tumor stage (p values 0.03 and 0.01, respectively).
Conclusion:
EGFR
and
HER2/neu
may play a limited role in prostatic adenocarcinoma as they showed positive expression in a limited number of the examined tissues specifically HER2neu. The expression of non-phosphorylated
ERK
(mostly weak to moderate) and phosphorylated
ERK
(mostly moderate to strong)- was appreciated in most cases. Thus, we suggest that anti-
EGFR
drugs may have a limited role in the treatment of castrate-resistant prostate cancer, but anti-MEK/
ERK
drugs may have more promising role as a target therapy. It is recommended to perform further molecular testing to elucidate the exact mechanism and significance of these markers.