Tendencies for higher co-expression of EGFR and HER2 and downregulation of HER3 in prostate cancer lymph node metastases compared with corresponding primary tumors

Abstract

Abstract. The epidermal growth factor receptor (EGFR) family members are potential targets for therapy using extracellular domain receptor binding agents, such as the antibodies trastuzumab and cetuximab, or antibodies labeled with therapeutically useful radionuclides or toxins. This is especially the case when the tumor cells are resistant to chemotherapy and tyrosine kinase inhibitors. Studies concerning the expression of these receptors in prostate cancer vary in the literature, possibly due to differences in patient inclusion, sample preparations and scoring criteria. In our study, EGFR, HER2 and HER3 expression was analyzed in prostate cancer samples from primary tumors and corresponding lymph node metastases from 12 patients. The expression of HER2 and EGFR was scored from immunohistochemical preparations and the HercepTest criteria (0, 1+, 2+ or 3+), while HER3 expression was scored as no, weak or strong staining. There were 5 EGFR-positive (2+ or 3+) primary tumors and 6 EGFR-positive lymph node metastases, and there was EGFR upregulation in one metastasis. Only 4 of the 12 patients had marked HER2 expression (2+ or 3+) in their primary tumors and there was one downregulation and 5 cases of upregulation in the metastases. Thus, a total of 8 out of 12 analyzed metastases were HER2-positive. Of the 12 primary tumors, 9 expressed HER3 while only 2 of the lymph node metastases expressed recognizable HER3 staining, so 7 metastases appeared to have downregulated HER3 expression.In one of the primary tumors there was positive co-expression of EGFR and HER2, while this co-expression was observed in 4 of the metastases. Thus, there were tendencies for upregulation of HER2, increased co-expression of EGFR and HER2 and downregulation of HER3 in the prostate cancer lymph node metastases in comparison to the primary tumors. The results are encouraging for studies involving more patients. Possible strategies for EGFR-and HER2-targeted therapy are briefly discussed in the present study, especially with regard to the expression and co-expression of EGFR and HER2 in metastases.

Expression of EGF receptors in canine prostate with proliferative inflammatory atrophy and carcinoma

“…These results are similar to those obtained by CARLSSON et al (2013) in their study with human PC and lymph node metastasis. They observed EGFR immunostaining in roughly 41% of primary tumors, and in one case of metastasis.…”

“…The samples were scored 1+, and considered negative. Faleiro et al CARLSSON et al (2013) reported that Her2 immunostaining may occur in normal tissues. Likewise, the IHC results concerning Her2 were in keeping with those obtained with RT-PCR technique, since there was no expression of ErbB2 in normal prostatic tissue.…”

“…It was also detected ErbB1 mRNA in 50% of these tissues. The authors GAMA et al (2009), PERALDO-NEIA et al (2011), andCARLSSON et al (2013), reported EGFR expression in normal tissues such as liver, digestive tract, human prostate, and canine mammary tissue. However, TERRAGNI et al (2014) reported no expression of EGFR in canine normal gastric epithelium, similar to what was observed here in 20% of canine normal prostatic tissue.…”

“…Thus, CARLSSON et al (2013) suggested that EGFR could have an important role in initial lesions of PC and it would be negligible in advanced-stage tumors.…”

“…Domains are activated through binding with the epidermal growth factor (EGF) or transforming growth factor alpha (TGF-α), which results in dimerization with Her1, or heterodimerization with another ErbB member. This leads to a receptor-linked tyrosine kinase activation and results in a signaling cascade that produces effects such as cell migration, maturation, differentiation, metastasis, angiogenesis, and inhibition of apoptosis (CARLSSON et al, 2013). EGFR is expressed or overexpressed in solid tumors, including PC.…”