Loss of SOX9 Expression Is Associated with PSA Recurrence in ERG-Positive and PTEN Deleted Prostate Cancers
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Loss of SOX9 Expression Is Associated with PSA Recurrence in ERG-Positive and PTEN Deleted Prostate Cancers. / Burdelski, Christoph; Bujupi, Erzen; Tsourlakis, Maria Christina; Hube-Magg, Claudia; Kluth, Martina; Melling, Nathaniel; Lebok, Patrick; Minner, Sarah; Koop, Christina; Graefen, Markus; Heinzer, Hans; Wittmer, Corinna; Sauter, Guido; Wilczak, Waldemar; Simon, Ronald; Schlomm, Thorsten; Steurer, Stefan; Krech, Till.
in: PLOS ONE, Jahrgang 10, Nr. 6, 2015, S. e0128525.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Loss of SOX9 Expression Is Associated with PSA Recurrence in ERG-Positive and PTEN Deleted Prostate Cancers
AU - Burdelski, Christoph
AU - Bujupi, Erzen
AU - Tsourlakis, Maria Christina
AU - Hube-Magg, Claudia
AU - Kluth, Martina
AU - Melling, Nathaniel
AU - Lebok, Patrick
AU - Minner, Sarah
AU - Koop, Christina
AU - Graefen, Markus
AU - Heinzer, Hans
AU - Wittmer, Corinna
AU - Sauter, Guido
AU - Wilczak, Waldemar
AU - Simon, Ronald
AU - Schlomm, Thorsten
AU - Steurer, Stefan
AU - Krech, Till
PY - 2015
Y1 - 2015
N2 - The transcription factor SOX9 plays a crucial role in normal prostate development and has been suggested to drive prostate carcinogenesis in concert with PTEN inactivation. To evaluate the clinical impact of SOX9 and its relationship with key genomic alterations in prostate cancer, SOX9 expression was analyzed by immunohistochemistry on a tissue microarray containing 11,152 prostate cancers. Data on ERG status and deletions of PTEN, 3p13, 5q21 and 6q15 were available from earlier studies. SOX9 expression levels were comparable in luminal cells of normal prostate glands (50% SOX9 positive) and 3,671 cancers lacking TMPRSS2:ERG fusion (55% SOX9 positive), but was markedly increased in 3,116 ERG-fusion positive cancers (81% SOX9 positive, p<0.0001). While no unequivocal changes in the SOX9 expression levels were found in different stages of ERG-negative cancers, a gradual decrease of SOX9 paralleled progression to advanced stage, high Gleason grade, metastatic growth, and presence of PTEN deletions in ERG-positive cancers (p<0.0001 each). SOX9 levels were unrelated to deletions of 3p, 5q, and 6q. Down-regulation of SOX9 expression was particularly strongly associated with PSA recurrence in ERG-positive tumors harboring PTEN deletions (p=0.001), but had no significant effect in ERG-negative cancers or in tumors with normal PTEN copy numbers. In summary, the results of our study argue against a tumor-promoting role of SOX9 in prostate cancer, but demonstrate that loss of SOX9 expression characterizes a particularly aggressive subset of ERG positive cancers harboring PTEN deletions.
AB - The transcription factor SOX9 plays a crucial role in normal prostate development and has been suggested to drive prostate carcinogenesis in concert with PTEN inactivation. To evaluate the clinical impact of SOX9 and its relationship with key genomic alterations in prostate cancer, SOX9 expression was analyzed by immunohistochemistry on a tissue microarray containing 11,152 prostate cancers. Data on ERG status and deletions of PTEN, 3p13, 5q21 and 6q15 were available from earlier studies. SOX9 expression levels were comparable in luminal cells of normal prostate glands (50% SOX9 positive) and 3,671 cancers lacking TMPRSS2:ERG fusion (55% SOX9 positive), but was markedly increased in 3,116 ERG-fusion positive cancers (81% SOX9 positive, p<0.0001). While no unequivocal changes in the SOX9 expression levels were found in different stages of ERG-negative cancers, a gradual decrease of SOX9 paralleled progression to advanced stage, high Gleason grade, metastatic growth, and presence of PTEN deletions in ERG-positive cancers (p<0.0001 each). SOX9 levels were unrelated to deletions of 3p, 5q, and 6q. Down-regulation of SOX9 expression was particularly strongly associated with PSA recurrence in ERG-positive tumors harboring PTEN deletions (p=0.001), but had no significant effect in ERG-negative cancers or in tumors with normal PTEN copy numbers. In summary, the results of our study argue against a tumor-promoting role of SOX9 in prostate cancer, but demonstrate that loss of SOX9 expression characterizes a particularly aggressive subset of ERG positive cancers harboring PTEN deletions.
U2 - 10.1371/journal.pone.0128525
DO - 10.1371/journal.pone.0128525
M3 - SCORING: Journal article
C2 - 26030748
VL - 10
SP - e0128525
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 6
ER -