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Apurinic/apyrimidinic endonuclease 1 (APE1/Ref‐1) overexpression is an independent prognostic marker in prostate cancer without TMPRSS2:ERG fusion
Author(s) -
Juhnke Manuela,
Heumann Asmus,
Chirico Viktoria,
Höflmayer Doris,
Menz Anne,
Hinsch Andrea,
HubeMagg Claudia,
Kluth Martina,
Lang Dagmar S.,
MöllerKoop Christina,
Sauter Guido,
Simon Ronald,
Beyer Burkhard,
Pompe Raisa,
Thederan Imke,
Schlomm Thorsten,
Luebke Andreas M.
Publication year - 2017
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22670
Subject(s) - tmprss2 , prostate cancer , biology , tissue microarray , erg , fusion gene , pca3 , cancer research , prostate , xrcc1 , cancer , immunohistochemistry , pathology , oncology , gene , medicine , disease , immunology , genetics , retina , covid-19 , neuroscience , genotype , infectious disease (medical specialty) , single nucleotide polymorphism
Polymorphisms of the base excision repair gene APE1 may be associated with an increased risk for developing prostate cancer. In other cancer types, altered APE1 protein expression is a candidate prognostic marker. Using immunohistochemistry, we thus analyzed APE1 expression in 9763 prostate cancers in a tissue microarray (TMA) with attached clinical and molecular data. The comparison with normal prostate tissue revealed an upregulation of APE1 in cancer samples. APE1 immunostaining was considered weak in 20.2%, moderate in 36.7%, and strong in 33.4% of cancers. Strong APE1 expression was markedly more frequent in prostate cancers harboring the TMPRSS2:ERG fusion (52.9%) than in ERG ‐ negative cancers (19.1%, P < 0.0001). Significant associations with Gleason grade, tumor stage, tumor grade, and early biochemical recurrence ( P < 0.0001 each) were largely limited to ERG‐negative tumors. Multivariable analysis revealed that the prognostic value of APE1 upregulation in ERG‐negative prostate cancers was independent from established histopathological and clinical parameters. In conclusion, the results of our study demonstrate that APE1 overexpression is an independent prognostic marker, but exclusively in ERG‐negative prostate cancers.