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Loss of pSer2448‐mTOR expression is linked to adverse prognosis and tumor progression in ERG‐fusion‐positive cancers
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| Zeitschriftentitel: | International Journal of Cancer |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , |
| In: | International Journal of Cancer, 132, 2013, 6, S. 1333-1340 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
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| Schlagwörter: |
| author_facet |
Müller, Julia Ehlers, Arne Burkhardt, Lia Sirma, Hüseyin Steuber, Thomas Graefen, Markus Sauter, Guido Minner, Sarah Simon, Ronald Schlomm, Thorsten Michl, Uwe Müller, Julia Ehlers, Arne Burkhardt, Lia Sirma, Hüseyin Steuber, Thomas Graefen, Markus Sauter, Guido Minner, Sarah Simon, Ronald Schlomm, Thorsten Michl, Uwe |
|---|---|
| author |
Müller, Julia Ehlers, Arne Burkhardt, Lia Sirma, Hüseyin Steuber, Thomas Graefen, Markus Sauter, Guido Minner, Sarah Simon, Ronald Schlomm, Thorsten Michl, Uwe |
| spellingShingle |
Müller, Julia Ehlers, Arne Burkhardt, Lia Sirma, Hüseyin Steuber, Thomas Graefen, Markus Sauter, Guido Minner, Sarah Simon, Ronald Schlomm, Thorsten Michl, Uwe International Journal of Cancer Loss of pSer2448‐mTOR expression is linked to adverse prognosis and tumor progression in ERG‐fusion‐positive cancers Cancer Research Oncology |
| author_sort |
müller, julia |
| spelling |
Müller, Julia Ehlers, Arne Burkhardt, Lia Sirma, Hüseyin Steuber, Thomas Graefen, Markus Sauter, Guido Minner, Sarah Simon, Ronald Schlomm, Thorsten Michl, Uwe 0020-7136 1097-0215 Wiley Cancer Research Oncology http://dx.doi.org/10.1002/ijc.27768 <jats:title>Abstract</jats:title><jats:p>Prevalence and clinical significance of mammalian target of rapamycin (mTOR) phosphorylation at the serine 2448 is disputed in prostate cancer. A tissue microarray containing 3,261 prostate cancers and 49 normal prostate samples with clinical follow‐up data was analyzed for p<jats:sup>Ser2448</jats:sup>‐mTOR expression by immunohistochemistry. Moderate to strong p<jats:sup>Ser2448</jats:sup>‐mTOR staining was found in all (<jats:italic>n</jats:italic> = 49) normal prostate tissues, but was lost in 24% or weak in 29% cancers. Moderate and strong staining was found in 36 and 11% of tumors. Loss of p<jats:sup>Ser2448</jats:sup>‐mTOR staining was significantly linked to advanced stage (<jats:italic>p</jats:italic> = 0.0027), high‐grade (<jats:italic>p</jats:italic> = 0.0045), nodal positive cancers (<jats:italic>p</jats:italic> = 0.0483), early tumor recurrence (<jats:italic>p</jats:italic> < 0.0001, independently from stage and grade, <jats:italic>p</jats:italic> = 0.0016), lack of Ets‐related gene (ERG) fusion (<jats:italic>p</jats:italic> < 0.0001), reduced androgen receptor expression (<jats:italic>p</jats:italic> < 0.0001 each) and increased cell proliferation (<jats:italic>p</jats:italic> = 0.0092) in all cancers and in the subset of ERG‐fusion‐positive cancers. Loss of p<jats:sup>Ser2448</jats:sup>‐mTOR expression was linked to tumor metastasis (<jats:italic>p</jats:italic> = 0.0275) in ERG‐fusion‐positive cancers only. Molecular subset analysis using pre‐existing phosphatase and tensin homolog (PTEN) deletion data revealed that loss of p<jats:sup>Ser2448</jats:sup>‐mTOR expression is of prognostic relevance and defines a subpopulation of PTEN‐deleted and ERG‐fusion‐positive cancers with a particular poor outcome. The results of our study strongly suggest that loss of p<jats:sup>Ser2448</jats:sup>‐mTOR expression is a marker for activated AKT/mTOR signaling. Tumors with concomitant PTEN deletion and activated mTOR signaling indicated by loss of p<jats:sup>Ser2448</jats:sup>‐mTOR expression characterize a small (4%) but clinically significant subset of prostate cancers that might optimally benefit from anti‐mTOR therapies.</jats:p> Loss of p<sup>Ser2448</sup>‐mTOR expression is linked to adverse prognosis and tumor progression in <i>ERG</i>‐fusion‐positive cancers International Journal of Cancer |
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| title |
Loss of pSer2448‐mTOR expression is linked to adverse prognosis and tumor progression in ERG‐fusion‐positive cancers |
| title_unstemmed |
Loss of pSer2448‐mTOR expression is linked to adverse prognosis and tumor progression in ERG‐fusion‐positive cancers |
| title_full |
Loss of pSer2448‐mTOR expression is linked to adverse prognosis and tumor progression in ERG‐fusion‐positive cancers |
| title_fullStr |
Loss of pSer2448‐mTOR expression is linked to adverse prognosis and tumor progression in ERG‐fusion‐positive cancers |
| title_full_unstemmed |
Loss of pSer2448‐mTOR expression is linked to adverse prognosis and tumor progression in ERG‐fusion‐positive cancers |
| title_short |
Loss of pSer2448‐mTOR expression is linked to adverse prognosis and tumor progression in ERG‐fusion‐positive cancers |
| title_sort |
loss of p<sup>ser2448</sup>‐mtor expression is linked to adverse prognosis and tumor progression in <i>erg</i>‐fusion‐positive cancers |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1002/ijc.27768 |
| publishDate |
2013 |
| physical |
1333-1340 |
| description |
<jats:title>Abstract</jats:title><jats:p>Prevalence and clinical significance of mammalian target of rapamycin (mTOR) phosphorylation at the serine 2448 is disputed in prostate cancer. A tissue microarray containing 3,261 prostate cancers and 49 normal prostate samples with clinical follow‐up data was analyzed for p<jats:sup>Ser2448</jats:sup>‐mTOR expression by immunohistochemistry. Moderate to strong p<jats:sup>Ser2448</jats:sup>‐mTOR staining was found in all (<jats:italic>n</jats:italic> = 49) normal prostate tissues, but was lost in 24% or weak in 29% cancers. Moderate and strong staining was found in 36 and 11% of tumors. Loss of p<jats:sup>Ser2448</jats:sup>‐mTOR staining was significantly linked to advanced stage (<jats:italic>p</jats:italic> = 0.0027), high‐grade (<jats:italic>p</jats:italic> = 0.0045), nodal positive cancers (<jats:italic>p</jats:italic> = 0.0483), early tumor recurrence (<jats:italic>p</jats:italic> < 0.0001, independently from stage and grade, <jats:italic>p</jats:italic> = 0.0016), lack of Ets‐related gene (ERG) fusion (<jats:italic>p</jats:italic> < 0.0001), reduced androgen receptor expression (<jats:italic>p</jats:italic> < 0.0001 each) and increased cell proliferation (<jats:italic>p</jats:italic> = 0.0092) in all cancers and in the subset of ERG‐fusion‐positive cancers. Loss of p<jats:sup>Ser2448</jats:sup>‐mTOR expression was linked to tumor metastasis (<jats:italic>p</jats:italic> = 0.0275) in ERG‐fusion‐positive cancers only. Molecular subset analysis using pre‐existing phosphatase and tensin homolog (PTEN) deletion data revealed that loss of p<jats:sup>Ser2448</jats:sup>‐mTOR expression is of prognostic relevance and defines a subpopulation of PTEN‐deleted and ERG‐fusion‐positive cancers with a particular poor outcome. The results of our study strongly suggest that loss of p<jats:sup>Ser2448</jats:sup>‐mTOR expression is a marker for activated AKT/mTOR signaling. Tumors with concomitant PTEN deletion and activated mTOR signaling indicated by loss of p<jats:sup>Ser2448</jats:sup>‐mTOR expression characterize a small (4%) but clinically significant subset of prostate cancers that might optimally benefit from anti‐mTOR therapies.</jats:p> |
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| description | <jats:title>Abstract</jats:title><jats:p>Prevalence and clinical significance of mammalian target of rapamycin (mTOR) phosphorylation at the serine 2448 is disputed in prostate cancer. A tissue microarray containing 3,261 prostate cancers and 49 normal prostate samples with clinical follow‐up data was analyzed for p<jats:sup>Ser2448</jats:sup>‐mTOR expression by immunohistochemistry. Moderate to strong p<jats:sup>Ser2448</jats:sup>‐mTOR staining was found in all (<jats:italic>n</jats:italic> = 49) normal prostate tissues, but was lost in 24% or weak in 29% cancers. Moderate and strong staining was found in 36 and 11% of tumors. Loss of p<jats:sup>Ser2448</jats:sup>‐mTOR staining was significantly linked to advanced stage (<jats:italic>p</jats:italic> = 0.0027), high‐grade (<jats:italic>p</jats:italic> = 0.0045), nodal positive cancers (<jats:italic>p</jats:italic> = 0.0483), early tumor recurrence (<jats:italic>p</jats:italic> < 0.0001, independently from stage and grade, <jats:italic>p</jats:italic> = 0.0016), lack of Ets‐related gene (ERG) fusion (<jats:italic>p</jats:italic> < 0.0001), reduced androgen receptor expression (<jats:italic>p</jats:italic> < 0.0001 each) and increased cell proliferation (<jats:italic>p</jats:italic> = 0.0092) in all cancers and in the subset of ERG‐fusion‐positive cancers. Loss of p<jats:sup>Ser2448</jats:sup>‐mTOR expression was linked to tumor metastasis (<jats:italic>p</jats:italic> = 0.0275) in ERG‐fusion‐positive cancers only. Molecular subset analysis using pre‐existing phosphatase and tensin homolog (PTEN) deletion data revealed that loss of p<jats:sup>Ser2448</jats:sup>‐mTOR expression is of prognostic relevance and defines a subpopulation of PTEN‐deleted and ERG‐fusion‐positive cancers with a particular poor outcome. The results of our study strongly suggest that loss of p<jats:sup>Ser2448</jats:sup>‐mTOR expression is a marker for activated AKT/mTOR signaling. Tumors with concomitant PTEN deletion and activated mTOR signaling indicated by loss of p<jats:sup>Ser2448</jats:sup>‐mTOR expression characterize a small (4%) but clinically significant subset of prostate cancers that might optimally benefit from anti‐mTOR therapies.</jats:p> |
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| spelling | Müller, Julia Ehlers, Arne Burkhardt, Lia Sirma, Hüseyin Steuber, Thomas Graefen, Markus Sauter, Guido Minner, Sarah Simon, Ronald Schlomm, Thorsten Michl, Uwe 0020-7136 1097-0215 Wiley Cancer Research Oncology http://dx.doi.org/10.1002/ijc.27768 <jats:title>Abstract</jats:title><jats:p>Prevalence and clinical significance of mammalian target of rapamycin (mTOR) phosphorylation at the serine 2448 is disputed in prostate cancer. A tissue microarray containing 3,261 prostate cancers and 49 normal prostate samples with clinical follow‐up data was analyzed for p<jats:sup>Ser2448</jats:sup>‐mTOR expression by immunohistochemistry. Moderate to strong p<jats:sup>Ser2448</jats:sup>‐mTOR staining was found in all (<jats:italic>n</jats:italic> = 49) normal prostate tissues, but was lost in 24% or weak in 29% cancers. Moderate and strong staining was found in 36 and 11% of tumors. Loss of p<jats:sup>Ser2448</jats:sup>‐mTOR staining was significantly linked to advanced stage (<jats:italic>p</jats:italic> = 0.0027), high‐grade (<jats:italic>p</jats:italic> = 0.0045), nodal positive cancers (<jats:italic>p</jats:italic> = 0.0483), early tumor recurrence (<jats:italic>p</jats:italic> < 0.0001, independently from stage and grade, <jats:italic>p</jats:italic> = 0.0016), lack of Ets‐related gene (ERG) fusion (<jats:italic>p</jats:italic> < 0.0001), reduced androgen receptor expression (<jats:italic>p</jats:italic> < 0.0001 each) and increased cell proliferation (<jats:italic>p</jats:italic> = 0.0092) in all cancers and in the subset of ERG‐fusion‐positive cancers. Loss of p<jats:sup>Ser2448</jats:sup>‐mTOR expression was linked to tumor metastasis (<jats:italic>p</jats:italic> = 0.0275) in ERG‐fusion‐positive cancers only. Molecular subset analysis using pre‐existing phosphatase and tensin homolog (PTEN) deletion data revealed that loss of p<jats:sup>Ser2448</jats:sup>‐mTOR expression is of prognostic relevance and defines a subpopulation of PTEN‐deleted and ERG‐fusion‐positive cancers with a particular poor outcome. The results of our study strongly suggest that loss of p<jats:sup>Ser2448</jats:sup>‐mTOR expression is a marker for activated AKT/mTOR signaling. Tumors with concomitant PTEN deletion and activated mTOR signaling indicated by loss of p<jats:sup>Ser2448</jats:sup>‐mTOR expression characterize a small (4%) but clinically significant subset of prostate cancers that might optimally benefit from anti‐mTOR therapies.</jats:p> Loss of p<sup>Ser2448</sup>‐mTOR expression is linked to adverse prognosis and tumor progression in <i>ERG</i>‐fusion‐positive cancers International Journal of Cancer |
| spellingShingle | Müller, Julia, Ehlers, Arne, Burkhardt, Lia, Sirma, Hüseyin, Steuber, Thomas, Graefen, Markus, Sauter, Guido, Minner, Sarah, Simon, Ronald, Schlomm, Thorsten, Michl, Uwe, International Journal of Cancer, Loss of pSer2448‐mTOR expression is linked to adverse prognosis and tumor progression in ERG‐fusion‐positive cancers, Cancer Research, Oncology |
| title | Loss of pSer2448‐mTOR expression is linked to adverse prognosis and tumor progression in ERG‐fusion‐positive cancers |
| title_full | Loss of pSer2448‐mTOR expression is linked to adverse prognosis and tumor progression in ERG‐fusion‐positive cancers |
| title_fullStr | Loss of pSer2448‐mTOR expression is linked to adverse prognosis and tumor progression in ERG‐fusion‐positive cancers |
| title_full_unstemmed | Loss of pSer2448‐mTOR expression is linked to adverse prognosis and tumor progression in ERG‐fusion‐positive cancers |
| title_short | Loss of pSer2448‐mTOR expression is linked to adverse prognosis and tumor progression in ERG‐fusion‐positive cancers |
| title_sort | loss of p<sup>ser2448</sup>‐mtor expression is linked to adverse prognosis and tumor progression in <i>erg</i>‐fusion‐positive cancers |
| title_unstemmed | Loss of pSer2448‐mTOR expression is linked to adverse prognosis and tumor progression in ERG‐fusion‐positive cancers |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1002/ijc.27768 |