ERG overexpression plus SLC45A3 (prostein) and PTEN expression loss: Strong association of the triple hit phenotype with an aggressive pathway of prostate cancer progression

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  • dc.contributor.author Hernández Llodrà, Silviaca
  • dc.contributor.author Juanpere, Nuriaca
  • dc.contributor.author Muga, Silvia deca
  • dc.contributor.author Lorenzo Perez, Martaca
  • dc.contributor.author Gil Ortega, Joanca
  • dc.contributor.author Font Tello, Alba 1990-ca
  • dc.contributor.author Agell, Laiaca
  • dc.contributor.author Albero-González, Raquelca
  • dc.contributor.author Segalés, Lauraca
  • dc.contributor.author Merino, Joséca
  • dc.contributor.author Serrano, Laiaca
  • dc.contributor.author Fumadó Ciutat, Lluisca
  • dc.contributor.author Cecchini Rosell, Lluísca
  • dc.contributor.author Lloreta, Josep, 1958-ca
  • dc.date.accessioned 2018-03-21T08:06:02Z
  • dc.date.available 2018-03-21T08:06:02Z
  • dc.date.issued 2017
  • dc.description.abstract TMPRSS2 and SLC45A3 rearrangements may coexist in the same tumor. ERG rearrangements and PTEN loss are concomitant events in prostate cancer (PrCa), and can cooperate in progression. We have reported that mRNA expression of TMPRSS2-ERG and SLC45A3-ERG rearrangements plus PTEN loss define an aggressive tumor subset. The aim of this study has been to validate these results by immunohistochemistry in a large cohort of tumors. ERG, SLC45A3 and PTEN immunostaining and their association with pathological features and PSA progression-free survival were analyzed in 220 PrCa (PSMAR-Biobank, Barcelona, Spain). ERG protein expression was found in 46.8% and SLC45A3 and PTEN loss in 30% and 34% tumors, respectively. Single ERG positive immunostaining was associated with GS = 6 tumors (p = 0.016), double ERG+/PTEN loss with GS = 7 (p = 0.008) and Grade Group 2 (GG) or GG3 cases (p = 0.042), ERG+/SLC45A3 loss/PTEN loss ("triple hit") with GS ≥ 8 (p < 0.0001) and GG4 or GG5 tumors (p = 0.0003). None of GS = 6 nor = GG1 cases showed this combination. In the GS ≥ 8 group, ERG+ (p = 0.002), PTEN loss (p = 0.009) and "triple hit" (p = 0.003) were associated with Gleason pattern 3 component, and single SLC45A3 loss (p = 0.036) with GS ≥ 8 without pattern 3. The number of aberrant events and the triple hit were strongly associated with shorter PSA progression-free survival. In GS = 6 PrCa, single ERG+ was also associated with progression. ERG+ identifies a distinct pathway of PrCa. Additional assessment of PTEN and SLC45A3 adds relevant prognostic information. The triple hit phenotype (ERG+/SLC45A3 loss/PTEN loss) is associated with progression and could be used for patient stratification, treatment and follow-up.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Hernández-Llodra S, Juanpere N, de Muga S, Lorenzo M, Gil J, Font-Tello A et al. ERG overexpression plus SLC45A3 (prostein) and PTEN expression loss: Strong association of the triple hit phenotype with an aggressive pathway of prostate cancer progression. Oncotarget. 2017 May 26;8(43):74106-18. DOI: 10.18632/oncotarget.18266
  • dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.18266
  • dc.identifier.issn 1949-2553
  • dc.identifier.uri http://hdl.handle.net/10230/34219
  • dc.language.iso eng
  • dc.publisher Impact Journalsca
  • dc.relation.ispartof Oncotarget. 2017 May 26;8(43):74106-18
  • dc.rights © Hernández-Llodrà et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0) (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/3.0/
  • dc.subject.keyword ERG
  • dc.subject.keyword PTEN
  • dc.subject.keyword SLC45A3
  • dc.subject.keyword Progression
  • dc.subject.keyword Prostate cancer
  • dc.title ERG overexpression plus SLC45A3 (prostein) and PTEN expression loss: Strong association of the triple hit phenotype with an aggressive pathway of prostate cancer progressionca
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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