NDLI: P16 upregulation is linked to poor prognosis in ERG negative prostate cancer

Content Provider	Springer Nature Link
Author	Burdelski, Christoph Dieckmann, Tatsiana Heumann, Asmus Hube Magg, Claudia Kluth, Martina Beyer, Burkhard Steuber, Thomas Pompe, Raisa Graefen, Markus Simon, Ronald Minner, Sarah Tsourlakis, Maria Christina Koop, Christina Izbicki, Jakob Sauter, Guido Krech, Till Schlomm, Thorsten Wilczak, Waldemar Lebok, Patrick
Copyright Year	2016
Abstract	Altered expression of the p16 tumor suppressor is frequently found in prostate cancer, but its role for tumor development and patient prognosis is disputed. In order to clarify the prognostic role of p16 and to draw conclusions on interactions with key molecular features of prostate cancer, we studied p16 expression in a tissue microarray (TMA) with more than 12,400 prostate cancers and attached clinical, pathological, and molecular data such as ERG status and deletions of 3p13, 5q21, 6q15, and PTEN. p16 immunostaining was absent in non-neoplastic prostate cells but was found in 37 % of 9627 interpretable prostate cancers. Finding p16 expression in 58 % of ERG positive but in only 22 % of ERG negative cancers (p < 0.0001), highlights the known androgen-dependence of both genes. Significant associations between p16 upregulation and tumor phenotype or patient prognosis were strictly limited to the subset of ERG negative cancers. For example, p16 positivity increased from 15 % in Gleason ≤3 + 3 to 38 % in Gleason ≥4 + 4 cancers (p < 0.0001) and was associated with early PSA recurrence (p < 0.0001). p16 upregulation was strongly linked to deletions of PTEN (p < 0.0001), highlighting the interaction of both genes in growth control. In conclusion, p16 upregulation is a strong prognostic factor in ERG negative cancers. The strict limitation of its prognostic impact to a molecularly defined subgroup challenges the concept of molecular prognosis testing without considering molecular subtypes.
Starting Page	12655
Ending Page	12663
Page Count	9
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	37
Issue Number	9
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-07-21
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	p16 Prostate cancer Prognosis Tissue microarray Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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