Abstract
PTEN is the most commonly inactivated tumor suppressor gene in primary prostate cancer (PCa) and its loss is associated with poor clinical outcomes. ERG rearrangement is a genomic alteration frequently found in PCa and its prognostic significance has yielded mixed results. Although the association of PTEN and ERG biomarkers has potential impact on clinical outcomes, studies examining the two genes simultaneously are scarce in Brazilian populations. In this study, we retrospectively examined the relationship between ERG expression and PTEN loss in 119 surgically treated prostate cancer patients from Northeastern Brazil through immunohistochemical analysis. ERG expression was found in 41.0% (48/117) of cases and the loss of PTEN detected in 38.1% (40/105) of samples. ERG-positive cases were significantly associated with lower prostate weight; ERG negatively correlated with Gleason score above 6. The lack of associations for PTEN loss alone in this cohort is counter to the literature, which shows that PTEN loss is usually associated with more aggressive disease. The overlapping of the two biomarkers revealed that samples with positive ERG expression without PTEN loss were associated with lower Gleason and lower Grade group. This study contributes with the discussion about the development of the molecular profiling of prostate cancer. The further development of similar studies could help in stratifying specific risk groups, leading to a more personalized therapeutic decision for prostate cancer treatment.
Highlights
The burden of prostate cancer (PCa) on male health is evident as it is one of the leading causes of cancer-related death among men worldwide [1]
Considering the relevance of race/ethnicity to the outcome of the disease, we studied the utility of two biomarkers, phosphatase tensin homolog (PTEN) and ETS-related gene (ERG), in a population of PCa patients from Northeastern Brazil, a diverse geographical region with no previous study
We evaluated ERG by IHC, a method that highly correlates with fluorescent in situ hybridization (FISH) as demonstrated by previous reports [22,23]
Summary
The burden of prostate cancer (PCa) on male health is evident as it is one of the leading causes of cancer-related death among men worldwide [1]. In Brazil, 14,500 deaths by PCa are registered annually and 68,220 new cases were estimated in 2018 [2] These numbers highlight the need for novel treatment approaches and prevention of PCa. Gleason score system, serum prostate-specific antigen (PSA), and clinical and pathological tumor stage are established tools for grading PCa, they are not capable of distinguishing men with high risk disease from the indolent majority. Patients on active surveillance may lose the correct timing for treatment or suffer from unnecessary side effects of overtreatment [3] To overcome these issues, a lot of approaches are being explored, such as molecular biomarkers aiming to give information about the tumor biology and help predict the course of the disease. Phosphatase tensin homolog (PTEN), an oncogene suppressor, and TMPRSS2-ERG, a gene rearrangement, are some of the most studied
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