title: High mitochondria content is associated with prostate cancer disease progression.
abstract: BACKGROUND
  Mitochondria are suggested to be important organelles for cancer initiation and promotion. This study was designed to evaluate the prognostic value of MTC02, a marker for mitochondrial content, in prostate cancer.
  
  
  METHODS
  Immunohistochemistry of using an antibody against MTC02 was performed on a tissue microarray (TMA) containing 11,152 prostate cancer specimens. Results were compared to histological phenotype, biochemical recurrence, ERG status and other genomic deletions by using our TMA attached molecular information.
  
  
  RESULTS
  Tumor cells showed stronger MTC02 expression than normal prostate epithelium. MTC02 immunostaining was found in 96.5% of 8,412 analyzable prostate cancers, including 15.4% tumors with weak, 34.6% with moderate, and 46.5% with strong expression. MTC02 expression was associated with advanced pathological tumor stage, high Gleason score, nodal metastases (p < 0.0001 each), positive surgical margins (p = 0.0005), and early PSA recurrence (p < 0.0001) if all cancers were jointly analyzed. Tumors harboring ERG fusion showed higher expression levels than those without (p < 0.0001). In ERG negative prostate cancers, strong MTC02 immunostaining was linked to deletions of PTEN, 6q15, 5q21, and early biochemical recurrence (p < 0.0001 each). Moreover, multiple scenarios of multivariate analyses suggested an independent association of MTC02 with prognosis in preoperative settings.
  
  
  CONCLUSIONS
  Our study demonstrates high-level MTC02 expression in ERG negative prostate cancers harboring deletions of PTEN, 6q15, and 5q21. Additionally, increased MTC02 expression is a strong predictor of poor clinical outcome in ERG negative cancers, highlighting a potentially important role of elevated mitochondrial content for prostate cancer cell biology.
authors.forename: Katharina
authors.initials: K
authors.lastname: Grupp
authors.forename: Karolina
authors.initials: K
authors.lastname: Jedrzejewska
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr, 52, 20246 Hamburg, Germany. mtsourlakis@uke.de.
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Tsourlakis
authors.forename: Christina
authors.initials: C
authors.lastname: Koop
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wilczak
authors.forename: Meike
authors.initials: M
authors.lastname: Adam
authors.forename: Alexander
authors.initials: A
authors.lastname: Quaas
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Jakob Robert
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.forename: Stefan
authors.initials: S
authors.lastname: Steurer
mesh_terms: D000368:Aged; D049109:Cell Proliferation; D018450:Disease Progression; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D015999:Multivariate Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics; D011379:Prognosis; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology*; D017384:Sequence Deletion; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000235:genetics; D000071230:Transcriptional Regulator ERG
chemical_list: C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human