title: Strong expression of the neuronal transcription factor FOXP2 is linked to an increased risk of early PSA recurrence in ERG fusion-negative cancers.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Pathology, University Medical Center, Hamburg-Eppendorf, Germany
authors.forename: Laura
authors.initials: L
authors.lastname: Stumm
authors.forename: Lia
authors.initials: L
authors.lastname: Burkhardt
authors.forename: Stefan
authors.initials: S
authors.lastname: Steurer
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Meike
authors.initials: M
authors.lastname: Adam
authors.forename: Andreas
authors.initials: A
authors.lastname: Becker
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Sirma
authors.forename: Uwe
authors.initials: U
authors.lastname: Michl
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012307:Risk Factors; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors; D019394:Ki-67 Antigen; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D017430:Prostate-Specific Antigen
keywords: Cancer research; Prostate; Tumour markers