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Molecular and Clinicopathological Aspects of Prostate Cancer in Bulgarian Probands

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Pathology & Oncology Research

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.

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Abbreviations

ADT:

Androgen deprivation therapy

BPH:

Benign prostatic hyperplasia

CNS:

Central nervous system

CRPC:

Castration-resistant prostate cancer

DNA:

Deoxyribonucleic acid

DRE:

Digital rectal examination

GS:

Gleason score

GWAS:

Genome wide association studies

mRNA:

Messenger Ribonucleic Acid

PCa:

Prostate cancer

PCR:

Polymerase Chain Reaction

PIA:

Proliferative inflammatory atrophy

PIN:

Prostatic intraepithelial neoplasia

PSA:

Prostate-Specific Antigen

qPCR:

Quantitative Polymerase Chain Reaction

RNA:

Ribonucleic Acid

SNP:

Single nucleotide polymorphism

TNM:

Tumor Node Metastasis

TURP:

Transurethral Resection of the Prostate

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Acknowledgments

This study was supported by the grants №4-D/2011 and 26-D/2012, and 17-D/2013 Medical University Sofia, Bulgaria.

Conflict of Interest

The authors report no conflict of interest.

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Authors and Affiliations

  1. Department of Medical Chemistry and Biochemistry, Medical University, Sofia, Bulgaria

    Anita Tsvetkova, Albena Todorova & Vanyo Mitev

  2. Genetic Medico-Diagnostic Laboratory “Genica”, Sofia, Bulgaria

    Anita Tsvetkova, Albena Todorova & Tihomir Todorov

  3. Department of Urology, Military Medical Academy, Sofia, Bulgaria

    Georgi Georgiev

  4. Department of Pathology, Military Medical Academy, Sofia, Bulgaria

    Ivanka Drandarska

Authors
  1. Anita Tsvetkova
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  2. Albena Todorova
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  3. Tihomir Todorov
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  4. Georgi Georgiev
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  5. Ivanka Drandarska
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  6. Vanyo Mitev
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Correspondence to Anita Tsvetkova.

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Tsvetkova, A., Todorova, A., Todorov, T. et al. Molecular and Clinicopathological Aspects of Prostate Cancer in Bulgarian Probands. Pathol. Oncol. Res. 21, 969–976 (2015). https://doi.org/10.1007/s12253-015-9915-x

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  • DOI: https://doi.org/10.1007/s12253-015-9915-x

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