ERG overexpression plus SLC45A3 (prostein) and PTEN expression loss: Strong association of the triple hit phenotype with an aggressive pathway of prostate cancer progression
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 aggressi...
| Autores: | , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2017 |
| País: | España |
| Institución: | Universitat Pompeu Fabra |
| Repositorio: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/34219 |
| Acceso en línea: | http://hdl.handle.net/10230/34219 http://dx.doi.org/10.18632/oncotarget.18266 |
| Access Level: | acceso abierto |
| Palabra clave: | ERG PTEN SLC45A3 Progression Prostate cancer |
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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 progressionHernández Llodrà, SilviaJuanpere, NuriaMuga, Silvia deLorenzo Perez, MartaGil Ortega, JoanFont Tello, Alba 1990-Agell, LaiaAlbero-González, RaquelSegalés, LauraMerino, JoséSerrano, LaiaFumadó Ciutat, LluisCecchini Rosell, LluísLloreta, Josep, 1958-ERGPTENSLC45A3ProgressionProstate cancerTMPRSS2 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.Impact Journals201820182017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/34219http://dx.doi.org/10.18632/oncotarget.18266reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésOncotarget. 2017 May 26;8(43):74106-18© 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.http://creativecommons.org/licenses/by/3.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/342192026-06-12T07:21:37Z |
| dc.title.none.fl_str_mv |
ERG overexpression plus SLC45A3 (prostein) and PTEN expression loss: Strong association of the triple hit phenotype with an aggressive pathway of prostate cancer progression |
| 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 |
| spellingShingle |
ERG overexpression plus SLC45A3 (prostein) and PTEN expression loss: Strong association of the triple hit phenotype with an aggressive pathway of prostate cancer progression Hernández Llodrà, Silvia ERG PTEN SLC45A3 Progression Prostate cancer |
| title_short |
ERG overexpression plus SLC45A3 (prostein) and PTEN expression loss: Strong association of the triple hit phenotype with an aggressive pathway of prostate cancer progression |
| title_full |
ERG overexpression plus SLC45A3 (prostein) and PTEN expression loss: Strong association of the triple hit phenotype with an aggressive pathway of prostate cancer progression |
| title_fullStr |
ERG overexpression plus SLC45A3 (prostein) and PTEN expression loss: Strong association of the triple hit phenotype with an aggressive pathway of prostate cancer progression |
| title_full_unstemmed |
ERG overexpression plus SLC45A3 (prostein) and PTEN expression loss: Strong association of the triple hit phenotype with an aggressive pathway of prostate cancer progression |
| title_sort |
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.creator.none.fl_str_mv |
Hernández Llodrà, Silvia Juanpere, Nuria Muga, Silvia de Lorenzo Perez, Marta Gil Ortega, Joan Font Tello, Alba 1990- Agell, Laia Albero-González, Raquel Segalés, Laura Merino, José Serrano, Laia Fumadó Ciutat, Lluis Cecchini Rosell, Lluís Lloreta, Josep, 1958- |
| author |
Hernández Llodrà, Silvia |
| author_facet |
Hernández Llodrà, Silvia Juanpere, Nuria Muga, Silvia de Lorenzo Perez, Marta Gil Ortega, Joan Font Tello, Alba 1990- Agell, Laia Albero-González, Raquel Segalés, Laura Merino, José Serrano, Laia Fumadó Ciutat, Lluis Cecchini Rosell, Lluís Lloreta, Josep, 1958- |
| author_role |
author |
| author2 |
Juanpere, Nuria Muga, Silvia de Lorenzo Perez, Marta Gil Ortega, Joan Font Tello, Alba 1990- Agell, Laia Albero-González, Raquel Segalés, Laura Merino, José Serrano, Laia Fumadó Ciutat, Lluis Cecchini Rosell, Lluís Lloreta, Josep, 1958- |
| author2_role |
author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
ERG PTEN SLC45A3 Progression Prostate cancer |
| topic |
ERG PTEN SLC45A3 Progression Prostate cancer |
| description |
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. |
| publishDate |
2017 |
| dc.date.none.fl_str_mv |
2017 2018 2018 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10230/34219 http://dx.doi.org/10.18632/oncotarget.18266 |
| url |
http://hdl.handle.net/10230/34219 http://dx.doi.org/10.18632/oncotarget.18266 |
| dc.language.none.fl_str_mv |
Inglés |
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Inglés |
| dc.relation.none.fl_str_mv |
Oncotarget. 2017 May 26;8(43):74106-18 |
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http://creativecommons.org/licenses/by/3.0/ info:eu-repo/semantics/openAccess |
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http://creativecommons.org/licenses/by/3.0/ |
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openAccess |
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Impact Journals |
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Impact Journals |
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reponame:Repositorio Digital de la UPF instname:Universitat Pompeu Fabra |
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