Loss of cytoplasmic survivin expression is an independent predictor of poor prognosis in radically operated prostate cancer patients

TY - JOUR

T1 - Loss of cytoplasmic survivin expression is an independent predictor of poor prognosis in radically operated prostate cancer patients

AU - Büscheck, Franziska

AU - Sulimankhil, Mariam

AU - Melling, Nathaniel

AU - Höflmayer, Doris

AU - Hube-Magg, Claudia

AU - Simon, Ronald

AU - Göbel, Cosima

AU - Hinsch, Andrea

AU - Weidemann, Sören

AU - Izbicki, Jacob R

AU - Jacobsen, Frank

AU - Mandelkow, Tim

AU - Blessin, Niclas C

AU - Möller-Koop, Christina

AU - Lutz, Florian

AU - Viehweger, Florian

AU - Möller, Katharina

AU - Sauter, Guido

AU - Lennartz, Maximillian

AU - Burandt, Eike

AU - Lebok, Patrick

AU - Minner, Sarah

AU - Bonk, Sarah

AU - Huland, Hartwig

AU - Graefen, Markus

AU - Schlomm, Thorsten

AU - Fraune, Christoph

N1 - © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

PY - 2020/2

Y1 - 2020/2

N2 - Survivin is an inhibitor of apoptosis. Aberrant survivin expression occurs in malignant tumors and has often been linked to unfavorable patient outcome. Here we analyzed 12 432 prostate cancers by immunohistochemistry. Survivin immunostaining was regularly expressed at high levels in normal prostate epithelium but expression was often reduced in prostate cancers. Among 9492 evaluable prostate cancers, 9% expressed survivin strongly, 19% moderately, 28% weakly, and 44% lacked it. Loss of cytoplasmic survivin was seen in advanced tumor stage, higher Gleason score, preoperative PSA levels, and Ki-67 labeling index, and associated with earlier PSA recurrence (P < .0001). Survivin loss was significantly more common in cancers carrying TMPRSS2:ERG fusions (61% survivin negative) than in ERG wild-type cancers (32% survivin negative; P < .0001). Multivariate analysis revealed that reduced cytoplasmic survivin expression predicted poor prognosis independent from Gleason score, pT, pN, and serum PSA level. This was valid for ERG-positive and ERG-negative cancers. Survivin expression loss even retained its prognostic impact in 1020 PTEN deleted cancers, a group that is already characterized by dismal patient prognosis. In conclusion, reduced survivin expression is associated with more aggressive tumors and inferior prognosis in prostate cancer.

AB - Survivin is an inhibitor of apoptosis. Aberrant survivin expression occurs in malignant tumors and has often been linked to unfavorable patient outcome. Here we analyzed 12 432 prostate cancers by immunohistochemistry. Survivin immunostaining was regularly expressed at high levels in normal prostate epithelium but expression was often reduced in prostate cancers. Among 9492 evaluable prostate cancers, 9% expressed survivin strongly, 19% moderately, 28% weakly, and 44% lacked it. Loss of cytoplasmic survivin was seen in advanced tumor stage, higher Gleason score, preoperative PSA levels, and Ki-67 labeling index, and associated with earlier PSA recurrence (P < .0001). Survivin loss was significantly more common in cancers carrying TMPRSS2:ERG fusions (61% survivin negative) than in ERG wild-type cancers (32% survivin negative; P < .0001). Multivariate analysis revealed that reduced cytoplasmic survivin expression predicted poor prognosis independent from Gleason score, pT, pN, and serum PSA level. This was valid for ERG-positive and ERG-negative cancers. Survivin expression loss even retained its prognostic impact in 1020 PTEN deleted cancers, a group that is already characterized by dismal patient prognosis. In conclusion, reduced survivin expression is associated with more aggressive tumors and inferior prognosis in prostate cancer.

U2 - 10.1002/cam4.2773

DO - 10.1002/cam4.2773

M3 - SCORING: Journal article

C2 - 31893572

VL - 9

SP - 1409

EP - 1418

JO - CANCER MED-US

JF - CANCER MED-US

SN - 2045-7634

IS - 4

ER -