Molecular characterization of prostate cancer in Middle Eastern population highlights differences with Western populations with prognostic implication

Abstract

Background: To investigate the incidence and prognostication of ERG, PTEN and SPINK1 protein expressions in prostate cancer cohort of Middle Eastern descent in comparison to published data from Western population.

Methods: Immunohistochemistry for ERG, PTEN and SPINK1 was performed in a cohort of localized PCA (n = 340). The data were correlated to pathological and clinical outcomes and compared to Western populations.

Results: ERG expression and PTEN loss were noted in 123/288 (42.7%) and 91/297 (30.6%) of patients, respectively. SPINK1 expression was assessed in a subset of cases, noted in 6/150 (4%) of patients. Only ERG expression was associated with grade groups, being more common in the lower grade groups (1-3 vs 4-5; p = 0.04). In contrast to the Western population, PTEN loss foci were more likely to be ERG negative, observed in 81% of tumor foci and patients with PTEN neg/ERG pos were more likely to exhibit biochemical recurrence (OR 2.831; 95% CI 1.10-726, p = 0.03). This association remained significant in multivariate analysis (OR 2.68; 95% CI 0.98-7.33, p = 0.05), after adjusting for GG, path stage and surgical margin.

Conclusion: This study documents significant differences in key molecular events in PCA in Middle Eastern population compared to Western populations that could explain differences in PCA incidence, progression and prognostication. ERG, PTEN and SPINK1 genomic alteration occur less frequently and the enrichment of ERG for PTEN loss is not observed. Additionally, patients with combined PTEN loss/ERG positive are at highest risk for BCR vs North American Caucasian population where PTEN loss alone seems to be associated with the worst clinical outcome. The data presented here further support differences in clonal evolution between Middle Eastern and Western population in relation to PCA and add further insight to understanding PCA molecular pathways.

Keywords: Biochemical recurrence; ERG protein expression; Gleason score; Middle eastern; PTEN; SPINK1; immunohistochemistry.

Fig. 1

a Immunohistochemistry for ERG positive (brown) and PTEN negative in Gleason grade group 1. b Immunohistochemistry for PTEN positive (purple) and ERG negative in Gleason grade group 1 (note endothelial cells staining brown for ERG acting as internal control). c Immunohistochemistry for ERG positive (brown) and PTEN positive (purple) in Gleason grade group 1. d Immunohistochemistry for SPINK1 positive (red) and ERG negative in Gleason grade group 1 (note endothelial cells staining brown for ERG acting as positive control)