Differential Immunoreactivity of Epidermal Growth Factor Receptor in Benign, Dysplastic and Malignant Prostatic Tissues

Abstract

To investigate epidermal growth factor receptor (EGFr) presence in the prostate, monoclonal antibody (clone EGFR1) immunohistochemical examination of radical prostatectomy specimens was performed (n = 37). All prostatic specimens contained benign prostatic hyperplasia (BPH) and/or dysplasia (prostatic intraepithelial neoplasia or PIN), as well as prostatic carcinoma (CaP). Areas of dysplasia were further categorized as to the basal cell layer and the luminal cell area. BPH, PIN, and CaP tissues in each specimen were analyzed by a single observer and graded on a scale from 0-4+. Fifteen samples were also analyzed for EGFr content utilizing a Cell Analysis Systems (CAS 200) image cytometer. EGFr immunoreactivity of BPH basal cells was significantly higher than EGFr immunoreactivity in areas of CaP (p < 0.001). EGFr staining of BPH basal cells was also significantly higher than that seen in PIN luminal cells (p < 0.001). Immunoreactivity of EGFr in PIN basal cells was significantly higher than in PIN luminal cells (p < 0.001). EGFr staining of basal cells in BPH tissues was higher than that seen in the PIN basal cell layer but the difference was not statistically significant (p = 0.06). The amount of staining present in PIN luminal cells was also significantly greater than in CaP tissues (p = 0.002). Quantitative image analysis utilizing the CAS 200 image cytometer was performed on BPH and CaP areas exclusively. EGFr immunoreactivity in basal cells of the BPH tissues was significantly greater than that seen in CaP tissues (p < 0.001). The decreased EGFr immunoreactivity in CaP may reflect a differentiating role for EGFr in normal tissues. Loss of EGFr influence may be associated with an increased proliferative state in PIN and CaP. Destruction or alteration of the epidermal grwoth factor receptor by a protease, such as prostatic specific antigen, may also explain our findings. At the present time the meaning of the different amounts of EGFr in the various types of prostate tissues is unknown.

Epidermal growth factor receptor activation in androgen-independent but not androgen-stimulated growth of human prostatic carcinoma cells

“…EGFR expression has also been correlated with higher histological grade, increased S-phase fraction and poorer prognosis of prostate cancers (Visacorpi et al, 1992). However, other immunohistochemical investigations have shown greater EGFR expression in normal and hyperplastic prostate compared with prostate cancer (Maygarden et al, 1992;Mellon et al, 1992;Ibrahim et al, 1993). Our study demonstrated a higher level of EGFR expression in the androgen-independent PC3 and DU145 cell lines than in LNCaP cells or in normal epithelial cells.…”

“…The EGFR and its ligands, EGF and TGF-a, have been identified in benign and malignant prostatic tissues and cells (Wilding et al, 1989; Connolly and Rose, 1991;Hofer et al, 1991;Fong et al, 1992;Maygarden et al, 1992;Ching et al, 1993;Ibrahim et al, 1993). The functional role of the TGF-a-EGFR interaction has been demonstrated in cultured prostate cancer cells (Hofer et al, 1991;Fong et al, 1992).…”

“…The epidermal growth factor receptor (EGFR) is a 170-kDa transmembrane glycoprotein that has been identified in normal, hyperplastic and malignant prostatic epithelium (Maygarden et al, 1992;Ching et al, 1993;Ibrahim et al, 1993). The binding of EGF, TGF-a or amphiregulin results in tyrosine phosphorylation of EGFR and activation of downstream signal transduction pathways (Aaronson, 1991;Pellicci et al, 1992; Leevers et al, 1994).…”

Molecular alterations of EGFR and PTEN in prostate cancer: association with high-grade and advanced-stage carcinomas

“…5,13,41,42 Data on the relationship between Gleason score and EGFR expression are also conflicting. [43][44][45] In recent papers, there is more agreement in the association between EGFR immunostaining and advanced adenocarcinoma stage, high Gleason score and preoperative PSA. These results support a role for EGFR expression in the development of prostate cancer and in the progression to an androgen-independent, hormone-refractory clinical phase.…”

TEAD1 and c-Cbl are novel prostate basal cell markers that correlate with poor clinical outcome in prostate cancer

“…c-Cbl belongs to a family of E3 ubiquitin ligases (Swaminathan and Tsygankov, 2006). It binds to and ubiquitinates a range of receptor tyrosine kinases including EGFR (de Melker et al, 2001) and MET (hepatocyte growth factor receptor) (Peschard et al, 2001), both of which are localised to the basal layer and have reported roles in prostate proliferation and differentiation (Ibrahim et al, 1993;Pisters et al, 1995;Knudsen and 2004; Schlomm et al, 2007). Receptor tyrosine kinases bound to c-Cbl are targeted to the endosomal compartment from where they are either trafficked to lysosomes for degradation or recycled back to the plasma membrane (Thien and Langdon, 2001).…”