Up regulation of the Hippo signalling effector YAP1 is linked to early biochemical recurrence in prostate cancers

TY - JOUR

T1 - Up regulation of the Hippo signalling effector YAP1 is linked to early biochemical recurrence in prostate cancers

AU - Marx, Andreas

AU - Schumann, Aljoscha

AU - Höflmayer, Doris

AU - Bady, Elena

AU - Hube-Magg, Claudia

AU - Möller, Katharina

AU - Tsourlakis, Maria Christina

AU - Steurer, Stefan

AU - Büscheck, Franziska

AU - Eichenauer, Till

AU - Clauditz, Till S

AU - Graefen, Markus

AU - Simon, Ronald

AU - Sauter, Guido

AU - Izbicki, Jakob R

AU - Huland, Hartwig

AU - Heinzer, Hans

AU - Haese, Alexander

AU - Schlomm, Thorsten

AU - Bernreuther, Christian

AU - Lebok, Patrick

AU - Polonski, Adam

PY - 2020/6/2

Y1 - 2020/6/2

N2 - The transcriptional coactivator YAP1 controls the balance between cell proliferation and apoptosis. YAP1 overexpression is linked to poor prognosis in many cancer types, yet its role in prostate cancer is unknown. Here, we applied YAP1 immunohistochemistry to a tissue microarray containing 17,747 clinical prostate cancer specimens. Cytoplasmic and nuclear YAP1 staining was seen in 81% and 63% of tumours. For both cytoplasmic and nuclear YAP1 staining, high levels were associated with advanced tumour stage, classical and quantitative Gleason grade, positive nodal stage, positive surgical margin, high KI67 labelling index, and early biochemical recurrence (p < 0.0001 each). The prognostic role of YAP1 staining was independent of established prognostic features in multivariate models (p < 0.001). Comparison with previously studied molecular markers identified associations between high YAP1 staining, TMPRSS2:ERG fusion (p < 0.0001), high androgen receptor (AR) expression (p < 0.0001), high Ki67 labelling index (p < 0.0001), and PTEN and 8p deletions (p < 0.0001 each). In conclusion, high YAP1 protein expression is an independent predictor of unfavourable disease course in prostate cancer. That cytoplasmic and nuclear YAP1 staining is equally linked to phenotype and prognosis fits well to a model where YAP1 activation during tumour progression includes up regulation, cytoplasmic accumulation and subsequent translocation to the nucleus.

AB - The transcriptional coactivator YAP1 controls the balance between cell proliferation and apoptosis. YAP1 overexpression is linked to poor prognosis in many cancer types, yet its role in prostate cancer is unknown. Here, we applied YAP1 immunohistochemistry to a tissue microarray containing 17,747 clinical prostate cancer specimens. Cytoplasmic and nuclear YAP1 staining was seen in 81% and 63% of tumours. For both cytoplasmic and nuclear YAP1 staining, high levels were associated with advanced tumour stage, classical and quantitative Gleason grade, positive nodal stage, positive surgical margin, high KI67 labelling index, and early biochemical recurrence (p < 0.0001 each). The prognostic role of YAP1 staining was independent of established prognostic features in multivariate models (p < 0.001). Comparison with previously studied molecular markers identified associations between high YAP1 staining, TMPRSS2:ERG fusion (p < 0.0001), high androgen receptor (AR) expression (p < 0.0001), high Ki67 labelling index (p < 0.0001), and PTEN and 8p deletions (p < 0.0001 each). In conclusion, high YAP1 protein expression is an independent predictor of unfavourable disease course in prostate cancer. That cytoplasmic and nuclear YAP1 staining is equally linked to phenotype and prognosis fits well to a model where YAP1 activation during tumour progression includes up regulation, cytoplasmic accumulation and subsequent translocation to the nucleus.

U2 - 10.1038/s41598-020-65772-w

DO - 10.1038/s41598-020-65772-w

M3 - SCORING: Journal article

C2 - 32488048

VL - 10

SP - 8916

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

IS - 1

ER -