ERG oncoprotein expression in prostate carcinoma patients of different ethnicities

Abstract

Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 (TMPRSS2)-ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed paraffin-embedded sections of transrectal ultrasound-guided prostate biopsy specimens, collected from 120 patients treated at the Sime Darby Medical Centre, Subang Jaya, Malaysia, were analyzed for ERG protein expression by immunohistochemistry using the anti-ERG monoclonal antibody 9FY as a surrogate for the detection of ERG fusion events. The overall frequency of ERG protein expression in the population evaluated in this study was 39.2%. Although seemingly similar to rates reported in other Asian communities, the expression of ERG was distinct amongst different ethnic groups (P=0.004). Malaysian Indian (MI) patients exhibited exceedingly high expression of ERG in their tumors, almost doubling that of Malaysian Chinese (MC) patients, whereas ERG expression was very low amongst Malay patients (12.5%). When collectively analyzing data, we observed a significant correlation between younger patients and higher ERG expression (P=0.04). The prevalence of ERG expression was significantly different amongst CaP patients of different ethnicities. The higher number of ERG-expressing tumors among MI patients suggested that the TMPRSS2-ERG fusion may be particularly important in the pathogenesis of CaP amongst this group of patients. Furthermore, the more frequent expression of ERG among the younger patients analyzed suggested an involvement of ERG in the early onset of CaP. The results of this study underline the value of using ERG status to better understand the differences in the etiology of CaP initiation and progression between ethnic groups.

Keywords: Malaysia; prostate cancer; serine 2-erythroblast transformation-specific-related gene fusion; transmembrane protease.

Figure 1

Erythroblast transformation-specific-related gene (ERG) oncoprotein expression of tumor sections from each patient examined. Heatmap representation of ERG expression in both patients and sections. Green, no expression; pink, low expression; peach, moderate expression; dark red, strong expression. Grey, no sections evaluated. MC, Malaysian Chinese; NS, not scored; MI, Malaysian Indian; MAL, Malay.

Figure 2

Immunohistochemical staining for the expression of erythroblast transformation-specific-related gene (ERG) oncoprotein using anti-ERG-MAb 9FY. Representative images showing (A) 0, negative; (B) 1+, mildly positive; (C) 2+, moderately positive; and (D) 3+, strongly positive staining for ERG expression.