title: Molecular and clinico-histological data in aggressive prostate cancer patients from Bulgaria.
abstract: OBJECTIVE
  Metastatic prostate cancer (PCa) is one of the leading causes of death in men worldwide. We report Bulgarian patients with strongly aggressive, castration-resistant PCa.
  
  
  METHODS
  PCA3 overexpression, GSTP1 promoter hyper-methylation, TMPRSS2-ERG gene fusions, IVS1-27G>A in the KLF6 gene and mutations in androgen receptor (AR) gene, for diagnostic purposes were assessed. PCR, real-time PCR (RT-PCR), sequencing, and bisulfite conversion of DNA were applied. We correlated the molecular data to the histological and clinical findings.
  
  
  RESULTS
  The obtained molecular profile in 11 PCa Bulgarian patients coincided with the clinico-histological data of strongly aggressive PCa. Association was detected between the tumor stage (assessed by TNM as T3 and T4) and the detected molecular profile of aggressive cancer behavior with one exception, assessed as T2. None of our patients had positive family history of prostate cancer and no somatic mutations were detected in the AR gene. All patients showed normal genotype with respect to the KLF6 IVS1- 27G>A polymorphism. The rest of the markers were positive in fresh prostatic tissues and biopsies from all patients, whereas only one blood sample showed triple positive result.
  
  
  CONCLUSIONS
  The appearance of PCa-specific markers in blood was considered as a predictor for a PCa (micro) dissemination into the circulation. The GSTP1 promoter hypermethylation is the earliest epigenetic alteration, which indicates cancerous changes and the first and long-lasting marker that is detectable in blood circulation. The molecular profile needs to be strictly monitored during treatment, which is of great help in determining the patient's individual response to therapy.
authors.affiliation: Department of Medical Chemistry and Biochemistry, Medical University Sofia, Bulgaria.
authors.forename: Anita
authors.initials: A
authors.lastname: Tsvetkova
authors.forename: Albena
authors.initials: A
authors.lastname: Todorova
authors.forename: Tihomir
authors.initials: T
authors.lastname: Todorov
authors.forename: Georgi
authors.initials: G
authors.lastname: Georgiev
authors.forename: Ivanka
authors.initials: I
authors.lastname: Drandarska
authors.forename: Vanyo
authors.initials: V
authors.lastname: Mitev
mesh_terms: D000368:Aged; D002031:Bulgaria; D019175:DNA Methylation; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi