title: Molecular and Clinicopathological Aspects of Prostate Cancer in Bulgarian Probands.
abstract: To correlate the molecular data to the clinicopathological parameters in Bulgarian prostate cancer patients. PCA3 overexpression, TMPRSS2-ERG gene fusion, GSTP1 promoter hypermethylation, somatic mutations in the AR gene and the IVS1-27G > A polymorphism in the KLF6 gene were studied. A total of 148 patients were analyzed: 16 aggressive PCa, 83 non-aggressive PCa, 25 BPH and 24 chronic inflammatory diseases. Real-time RT-PCR, DNA sequencing, and bisulfite conversion of DNA, were applied. All cases with aggressive PCa before treatment were tested positive for PCA3 overexpression, expression of a T2-ERG gene fusion product and GSTP1 promoter hypermethylation. No somatic mutations were detected in the AR gene and all patients showed normal KLF6-IVS1-27G > A genotype. The TMPRSS2-ERG positive status correlates with moderate to poorly differentiated prostate tumors and it is considered as unfavorable disease predictor. Positive GSTP1 promoter hypermethylation seems to be highly specific and the earliest epigenetic change in the prostate gland, which indicates the beginning of the pathological process. The appearance of positive molecular markers in blood was considered as a predictor of PCa dissemination. GSTP1 promoter hypermethylation was found as the earliest and a long-lasting epigenetic marker in blood samples of PCa patients, which makes it suitable as a marker for treatment follow-up. The molecular profile of prostate cancer needs to be strictly monitored during the course of disease treatment, which is of a great help in determining the patient's individual therapy response.
authors.affiliation: Department of Medical Chemistry and Biochemistry, Medical University, Sofia, Bulgaria, annita_25@abv.bg.
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: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002031:Bulgaria / Q000453:epidemiology; D019175:DNA Methylation; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011470:Prostatic Hyperplasia / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: C410798:AR protein, human; D014408:Biomarkers, Tumor; C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011944:Receptors, Androgen; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human