Association of ERG and TMPRSS2-ERG with grade, stage, and prognosis of prostate cancer is dependent on their expression levels.
BACKGROUND
There is controversy in the literature on the role of the fusion TMPRSS2-ERG in the pathogenesis and progression of prostate cancer. The quantitative differences in TMPRSS2-ERG fusion expression have received very limited attention in the literature.


METHODS
We have quantitatively analyzed the mRNA levels of TMPRSS2-ERG, ERG, PTEN, and AR (n = 83), as well as ERG immunostaining (n = 78) in a series of prostate tumors.


RESULTS
Among the TMPRSS2-ERG cases (n = 57), high fusion levels were associated with GS ≥8 (P = 0.025). ERG mRNA overexpression was associated with GS ≥8 (P = 0.047), and with stage T3-T4 tumors (P = 0.032). Among the ERG overexpressing cases (n = 54), higher expression levels were found in 92.3% of GS ≥8 tumors (P = 0.02). ERG immunostaining, regardless of staining intensity, was also associated with high stage (P = 0.05). There was a statistical association between ERG immunostaining and PSA progression-free survival (Log Rank test, P = 0.048). Decreased PTEN expression was associated with TMPRSS2-ERG (P = 0.01), ERG mRNA overexpression (P = 0.003) and ERG immunostaining (P = 0.007). Furthermore, decreased PTEN expression, alone (P = 0.041) and also combined with TMPRSS2-ERG (P = 0.04) or with ERG overexpression (P = 0.04) was associated with GS ≥7 tumors.


CONCLUSIONS
Although more studies are needed to further clarify their role, our findings emphasize that the expression levels of the TMPRSS2-ERG fusion and ERG mRNA, rather than their mere presence, are related to a more aggressive phenotype, have an effect on prognosis and could be molecular markers of progression for prostate cancer. Furthermore, ERG immunohistochemistry could be also a potentially useful prognostic factor.
Department of Pathology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.
Alba
A
Font-Tello
Department of Pathology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.|Department of Health and Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
Núria
N
Juanpere
Department of Health and Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
Silvia
S
de Muga
Department of Pathology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.
Marta
M
Lorenzo
Department of Urology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.|Autonomous University of Barcelona, Barcelona, Spain.
José A
JA
Lorente
Department of Urology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.|Autonomous University of Barcelona, Barcelona, Spain.
Lluis
L
Fumado
Department of Pathology, Hospital Universitari Germans Tries i Pujol, Barcelona, Spain.|Autonomous University of Barcelona, Barcelona, Spain.
Laia
L
Serrano
Department of Pathology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.|Autonomous University of Barcelona, Barcelona, Spain.
Sergio
S
Serrano
Department of Pathology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain.|Department of Health and Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
Josep
J
Lloreta
Department of Health and Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
Silvia
S
Hernández
D000368:Aged; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D050596:Oncogene Fusion; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D017430:Prostate-Specific Antigen
ERG; TMPRSS2-ERG; grade; prognosis; prostate cancer; stage