EGFR和HER2/neu作为生长因子受体的改变以及RAS/RAF/MAP激酶的细胞质信号转导蛋白,包括其末端效应分子(ERK)在许多肿瘤的致癌作用中很重要。前列腺癌中这些原癌基因的激活仍在研究中。这项工作的目的是研究EGFR,HER2-neu,与临床和病理参数相关的前列腺腺癌中无活性(非磷酸化)和活性(磷酸化)ERK表达。
方法:免疫组织化学-使用组织微阵列-用于EGFR,HER2/neu,非磷酸化,和荧光粉ERK,对166例未经治疗的原发性前列腺腺癌患者的组织进行了研究。将不同标志物表达结果与临床病理参数进行相关性分析。
结果:前列腺组织显示EGFR,HER2neu,磷酸化和非磷酸化ERK表达为8.4%,1.4%,78.2%,无论是低表达(斑片状)还是高表达(弥漫性),分别为83.4%。在患者特征和测试标志物的表达之间没有发现显著的相关性。非磷酸化ERK和EGFR-的负免疫反应性与高肿瘤分期显着相关(p值分别为0.03和0.01)。
结论:EGFR和HER2/neu可能在前列腺腺癌中起着有限的作用,因为它们在有限数量的检查组织中显示出阳性表达,特别是HER2neu。在大多数情况下,非磷酸化ERK(主要是弱到中等)和磷酸化ERK(主要是中等到强)的表达受到赞赏。因此,我们认为抗EGFR药物在去势抵抗性前列腺癌的治疗中可能具有有限的作用,但抗MEK/ERK药物作为靶向治疗可能具有更有希望的作用.建议进行进一步的分子测试以阐明这些标记的确切机制和意义。
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).
CONCLUSIONS: 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.