Detection of telomerase activity in prostate massage samples improves differentiating prostate cancer from benign prostatic hyperplasia



We performed a case-control study in which we tested the ability of a non-invasive assay to detect telomerase activity and to distinguish between prostatic cancer (Pca) and benign prostatic hyperplasia (BPH) on samples of epithelial cells obtained after prostatic massage.


Telomerase activity was determined by a telomeric repeat amplification protocol (TRAP) assay. We selected 60 patients with histologically proven Pca (30 cases) or BPH (30 cases). Specimens included in this study were from patients who had no suspicious findings on digital rectal examination for cancer, had clinical evidence of lower urinary tract symptoms, had no sonographic signs of Pca at the transrectal ultrasound evaluation, had total PSA values moderately elevated (2.6–15 ng/ml), and had no evidence of other urological cancers. The whole procedure was conducted in double blind between pathologists and molecular biology operators.


Telomerase activity was detected in 90% of Pca cases and in 13% of BPH cases. The sensitivity (90%) and specificity (76%) of this method were calculated. The positive predictive value, negative predictive value, and diagnostic efficiency were 87%, 90%, and 88% respectively.


Our data indicate that telomerase activity detected by TRAP assay on prostate epithelial cells collected by prostate massage can substantially improve the distinction between Pca and BPH conditions. One of the clinical benefits resulting from the use of this new assay would be to refine the biopsy indication and to avoid for several patients without Pca the unnecessary cost and the complications of prostate biopsy.

This is a preview of subscription content, access via your institution.

Fig. 1


  1. Alivizatos G, Deliveliotis C, Mitropoulos D, Raptides G, Louras G, Karayiannis A, Becopoulos T, Dimopoulos AM (1996) Does free to total ratio of prostate specific antigen alter decision making on prostatic biopsy. Urology 48[Suppl 6A]:71–75

  2. Bangma CH, Rietbergen JB, Kranse R, Blijenberg BG, Petterson K, Schroder FH (1997) The free-to-total prostate-specific antigen ratio improves the specificity of prostate-specific antigen in screening for Pca in the general population. J Urol 157:2191–2196

    Article  CAS  PubMed  Google Scholar 

  3. Bettendorf O, Heine B, Kneif S, Eltze E, Semjonow A, Herbst H, Stein H, Bocker W, Poremba C (2003) Expression-patterns of the RNA component (hTR)and the catalytic subunit (hTERT) of human telomerase in nonneoplastic prostate tissue, prostatic intraepithelial neoplasia, and prostate cancer. Prostate 55:99–104

    Article  CAS  PubMed  Google Scholar 

  4. Blackburn EH (1991) Structure and function of telomerase. Nature 350:569–573

    CAS  PubMed  Google Scholar 

  5. Bologna M, Vicentini C, Festuccia C, Muzi P, Napolitano T, Biordi L, Miano L (1988) Early diagnosis of prostatic carcinoma based on in vitro culture of viable tumour cells harvested by prostatic massage. Eur Urol 14:474–476

    CAS  PubMed  Google Scholar 

  6. Bologna M, Vicentini C, Corrao G, Festuccia C, Muzi P, Tubaro A, Biordi L, Miano L (1993) Early diagnosis of prostatic carcinoma may be achieved through in vitro culture of tumour cells harvested by prostatic massage. Eur Urol 24:148–155

    CAS  PubMed  Google Scholar 

  7. Bologna M, Vicentini C, Muzi P, Festuccia C, Zazzeroni F, di Pasquale B, Valenti M, Corrao G (1995) Improved tissue culture method for the study of study of prostatic carcinoma:a significant diagnostic tool. Path Res Pract 191:899–903

    CAS  PubMed  Google Scholar 

  8. Caldarera E, Crooks NH, Muir GH, Pavone-Macaluso M, Carmichael PL (2000) An appraisal of telomerase activity in benign prostatic hyperplasia. Prostate 45:267–270

    Article  CAS  PubMed  Google Scholar 

  9. Catalona WJ, Smith DS, Ratliff TL, Dodds KM, Coplen DE, Yuan JJ, Petros JA, Andriole GL (1991) Measurement of prostate specific antigen in serum as a screening test for Pca. N Engl J Med 324:1156–1161

    CAS  PubMed  Google Scholar 

  10. Christensson A, Bjork T, Nilsson O, Dahlen U, Matikainen MT, Cockett AT, Abrahamsson PA, Lilja H (1993) Serum prostate specific antigen complex to alpha I-antichymotripsin as an indicator of Pca. J Urol 150:100–105

    CAS  PubMed  Google Scholar 

  11. Falchetti ML, Levi A, Molinari P, Verna R, D’Ambrosio E (1998) Increased sensitivity and reproducibility of TRAP assay by avoiding direct primers interaction. Nucleic Acids Res 26:862–863

    Article  CAS  PubMed  Google Scholar 

  12. Hiyama E, Kodama T, Shinbara K, Iwao T, Itoh M, Hiyama K, Shay JW, Matsuura Y, Yokoyama T (1997) Telomerase activity is detected in pancreatic cancer but not in benign tumors. Cancer Res 57:326–331

    CAS  PubMed  Google Scholar 

  13. Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011–2015

    CAS  PubMed  Google Scholar 

  14. Meid FH, Gygi CM, Leisinger HJ, Bosman FT, Benhattar J (2001) The use oftelomerase activity for the detection of prostatic cancer cells after prostatic massage. J Urol 165:1802–1805

    CAS  PubMed  Google Scholar 

  15. Neumann AA, Reddel RR (2002) Telomerase maintenance and cancer look, notelomerase. Nature Rev Cancer 2:879–884

    Article  CAS  Google Scholar 

  16. Poremba C, Shroyer KR, Frost M, Diallo R, Fogt F, Schafer KL, Burger H, Shroyer AL, Dockhorn-Dworniczak B, Boecker W (1999) Telomerase is a highly sensitive and specific molecular marker in fine-needle aspirates of breast lesions. J Clin Oncol 17:2020–2026

    CAS  PubMed  Google Scholar 

  17. Scates DK, Muir GH, Venitt S, Carmichael PL (1997) Detection of telomerase activity in human prostate:a diagnostic marker for prostatic cancer? Br J Urol 80:263–268

    Article  CAS  PubMed  Google Scholar 

  18. Scheel C, Schaefer KL, Jauch A, Keller M, Wai D, Brinkschmidt C, van Valen F, Boecker W, Dockhorn-Dworniczak B, Poremba C (2001) Alternative lengthening of telomeres is associated with chromosomal instability in osteosarcomas. Oncogene20:3835–3844

  19. Scheel C, Poremba C (2002) Telomere lengthening in telomerase-negative cells:the ends are coming together. Virchows Arch 440:573–582

    Article  CAS  PubMed  Google Scholar 

  20. Shay JW, Bacchetti S (1997) A survey of telomerase activity in human cancer. Eur J Cancer 33:787–791

    Article  CAS  PubMed  Google Scholar 

  21. Sommerfeld HJ, Meeker AK, Piatyszek MA, Bova GS, Shay JW, Coffey DS (1996)Telomerase activity: a prevalent marker of malignant human prostate tissue. Cancer Res 56:218–222

    CAS  PubMed  Google Scholar 

  22. Stenman UH, Leinonen J, Alfthan H, Rannikko S, Tuhkanen K, Alfthan O (1991) Complex between prostate specific antigen and alpha I-antichymotripsin is the major form of prostate specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer. Cancer Res 51:222–226

    CAS  PubMed  Google Scholar 

  23. Wang Z, Ramin SA, Tsai C, Lui P, Herbert PJ, Kyeyune-Nyombi E, Ruckle HC, Beltz RE, Sands JF (2000) Detection of telomerase activity in prostatic fluid specimens. Urol Oncol 6:4–9

    Article  PubMed  Google Scholar 

  24. Yang CT, Lee MH, Lan RS, Chen JK (1998) Telomerase activity in pleural effusions: diagnostic significance. J Clin Oncol 16:567–573

    CAS  PubMed  Google Scholar 

  25. Zhang W, Kapusta LR, Slingerland JM, Klotz LH (1998) Telomerase activity in prostate cancer, prostatic intraepithelial neoplasia, and benign prostatic epithelium. Cancer Res 58:619–621

    CAS  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Claudio Festuccia.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Vicentini, C., Gravina, G.L., Angelucci, A. et al. Detection of telomerase activity in prostate massage samples improves differentiating prostate cancer from benign prostatic hyperplasia. J Cancer Res Clin Oncol 130, 217–221 (2004).

Download citation


  • Telomerase
  • Prostate cancer
  • Prostate massage
  • TRAP activity
  • Early diagnosis