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Strong expression of the neuronal transcription factor FOXP2 is linked to an increased risk of early PSA recurrence in ERG fusion-negative cancers
  1. Laura Stumm1,
  2. Lia Burkhardt1,
  3. Stefan Steurer1,
  4. Ronald Simon1,
  5. Meike Adam2,
  6. Andreas Becker2,
  7. Guido Sauter1,
  8. Sarah Minner1,
  9. Thorsten Schlomm2,3,
  10. Hüseyin Sirma1,
  11. Uwe Michl2
  1. 1Institute of Pathology, University Medical Center, Hamburg-Eppendorf, Germany 
  2. 2Martini Clinic, Prostate Cancer Center, University Medical Center, Hamburg-Eppendorf, Germany
  3. 3Department of Urology, Section for Translational Prostate Cancer Research, University Medical Center, Hamburg-Eppendorf, Germany
  1. Correspondence to Uwe Michl, Martini-Clinic, Prostate Cancer Center, University Medical Center, 20246, Hamburg-Eppendorf, Germany; michl{at}uke.de

Abstract

Background and aims Transcription factors of the forkhead box P (FOXP1-4) family have been implicated in various human cancer types before. The relevance and role of neuronal transcription factor FOXP2 in prostate cancer is unknown.

Methods A tissue microarray containing samples from more than 11 000 prostate cancers from radical prostatectomy specimens with clinical follow-up data was analysed for FOXP2 expression by immunohistochemistry. FOXP2 data were also compared with pre-existing ERG fusion (by fluorescence in situ hybridisation and immunohistochemistry) and cell proliferation (Ki67 labelling index) data.

Results There was a moderate to strong FOXP2 protein expression in basal and secretory cells of normal prostatic glands. As compared with normal cells, FOXP2 expression was lost or reduced in 25% of cancers. Strong FOXP2 expression was linked to advanced tumour stage, high Gleason score, presence of lymph node metastases and early tumour recurrence (p<0.0001; each) in ERG fusion-negative, but not in ERG fusion-positive cancers. High FOXP2 expression was linked to high Ki67 labelling index (p<0.0001) in all cancers irrespective of ERG fusion status.

Conclusions These data demonstrate that similar high FOXP2 protein levels as in normal prostate epithelium exert a ‘paradoxical’ oncogenic role in ‘non fusion-type’ prostate cancer. It may be speculated that interaction of FOXP2 with members of pathways that are specifically activated in ‘non fusion-type’ cancers may be responsible for this phenomenon.

  • Cancer Research
  • Tumour Markers
  • Prostate

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