Abstract
ObjectivesThe aim of this study was to investigate the expression of two commonly altered genes ERG and PTEN in prostate cancer (PC) and evaluate their prognostic significance. Despite conflicting published results, TMPRSS2-ERG gene fusion and PTEN loss are generally considered unfavorable markers for PC progression.Materials and MethodsOf the 762 prostatic adenocarcinoma specimens obtained from radical prostatectomy, 613 without neoadjuvant hormone therapy were included in tissue microarrays for quantitatively assessment of ERG and PTEN expression via immunohistochemistry. Statistical analysis of the association between such expression and clinicopathological parameters, including clinical prognosis, was performed with a p-value of <0.05 considered significant.ResultsDuring a median follow-up period of 44.0 months, 132 (21.5%) patients developed biochemical recurrence (BCR). ERG overexpression and PTEN loss were observed in 145 (23.7%) and 253 (41.3%) cases, respectively. BCR-free survival was significantly better in patients with ERG overexpression (p=0.005), but unfavorable among those with PTEN loss (p=0.142). Sub-group analysis revealed that patients with PTEN loss and negative ERG expression had the worst BCR-free survival outcome (p=0.021). Furthermore, multivariate analysis identified prostate-specific antigen level (≥10 ng/mL), Gleason score (>6), pathologic T stage (≥T3), positive surgical margin, and extraprostatic capsule extension as significant risk factors for BCR (p<0.05).ConclusionsOur results indicated that ERG overexpression was associated with favorable BCR-free survival after radical prostatectomy for PC, whereas PTEN loss was with unfavorable outcomes.
Highlights
Prostate cancer (PC), the most prevalent cancer in men, is the second leading cause of male cancer death, in Western countries and in the Asia [1]
Of the 762 prostatic adenocarcinoma specimens obtained from radical prostatectomy, 613 without neoadjuvant hormone therapy were included in tissue microarrays for quantitatively assessment of ERG and PTEN expression via immunohistochemistry
biochemical recurrence (BCR)-free survival was significantly better in patients with ERG overexpression (p=0.005), but unfavorable among those with PTEN loss (p=0.142)
Summary
Prostate cancer (PC), the most prevalent cancer in men, is the second leading cause of male cancer death, in Western countries and in the Asia [1]. Despite diverse multimodality treatment options and extensive researches, PC remains a major health burden in men, and its diverse clinical outcomes regarding progression is a problem to be addressed owing to the disease’s heterogeneity Such a challenging diversity necessitates the proper stratification of patients according to risk factors, such as levels of prostate-specific antigen (PSA) and its derivatives, Gleason score, and disease stage. Previous studies have identified the TMPRSS2 (androgen-regulated transmembrane protease serine 2)-ERG gene fusion on chromosome 21 as the most common aberration and an important key driver in PC [3, 4]. The role of ERG in PC prognosis remains debatable to date, mostly owing to different reported clinical outcomes [7,8,9,10]
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