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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, Sílvia
dc.contributor.author Juanpere, Nuria
dc.contributor.author Muga, Silvia de
dc.contributor.author Lorenzo Perez, Marta
dc.contributor.author Gil Ortega, Joan
dc.contributor.author Font Tello, Alba 1990-
dc.contributor.author Agell, Laia
dc.contributor.author Albero-González, Raquel
dc.contributor.author Segalés, Laura
dc.contributor.author Merino, José
dc.contributor.author Serrano, Laia
dc.contributor.author Fumadó Ciutat, Lluis
dc.contributor.author Cecchini Rosell, Lluís
dc.contributor.author Lloreta Trull, Josep, 1958-
dc.date.accessioned 2018-03-21T08:06:02Z
dc.date.available 2018-03-21T08:06:02Z
dc.date.issued 2017
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):74106-74118. DOI: 10.18632/oncotarget.18266. eCollection 2017 Sep 26
dc.identifier.issn 1949-2553
dc.identifier.uri http://hdl.handle.net/10230/34219
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.language.iso eng
dc.publisher Impact Journals
dc.relation.ispartof Oncotarget. 2017 May 26;8(43):74106-74118
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.uri http://creativecommons.org/licenses/by/3.0/
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 progression
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.18266
dc.subject.keyword ERG
dc.subject.keyword PTEN
dc.subject.keyword SLC45A3
dc.subject.keyword Progression
dc.subject.keyword Prostate cancer
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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