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Clusterin as a possible predictor for biochemical recurrence of prostate cancer following radical prostatectomy with intermediate Gleason scores: a preliminary report

Abstract

Disease recurrence following radical prostatectomy is a major concern in prostate cancer patients. Gleason scores are useful in predicting recurrence. Low Gleason scores are usually associated with long disease-free intervals, while high Gleason scores are suggestive of early recurrence. However, prediction of recurrence has been difficult with intermediate Gleason scores. Clusterin is a ubiquitous secretory sulfated glycoprotein. It is also an antiapoptotic mediator in prostate cancer. The objective of the present study is to determine if clusterin can serve as a predictive biomarker for recurrence of prostate cancer with intermediate Gleason scores in patients following radical prostatectomy. Prostatic specimens with Gleason score of 6 (3+3) or 7 (3+4) were obtained from the archival bank. Three groups of specimens were investigated. The first group was from nine patients who developed recurrent disease according to a persistent rise of serum PSA within 3 years following radical prostatectomy. Those in the second group and the third group were from patients who showed no evidence of disease recurrence for at least 5 y (11 patients) and 10 y (eight patients), respectively following the surgery. Histological sections were subjected to immunohistochemical staining using a monoclonal antibody specific for clusterin. The staining intensity was scored as 0, 1, 2, and 3, with 0 being no staining, 1 showing less than 25% positive staining, 2 being 25–50% positive, and 3 showing greater than 75% positive staining. One-way ANOVA with Bonferroni correction was used for statistical analysis. Evaluation of the scores of clusterin staining was carried out according to four specific areas in each specimen. They were (a) benign epithelial cells, (b) malignant epithelial cells (cancer epithelia), (c) stromal cells surrounding benign cells, and (d) stromal cells surrounding malignant cells (cancer stroma). Staining score in prostatic epithelial cells, benign as well as malignant, showed no significant relationship among the three patient groups. However, when staining scores in stromal cells were compared, there was a significant difference between patients with recurrent disease and those showed no evidence of disease recurrence for at least 10 y. Results of this preliminary study support the important role of clusterin in the stromal component for prostate cancer progression. Clusterin immunostaining may be useful to aid the prediction of chance of disease recurrence in patients with Gleason score 6 or 7 prostate cancer following radical prostatectomy. Further studies with a large number of cases are warranted to verify this preliminary finding.

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References

  1. Croawford ED, Kiker JD . Radical retropubic prostatectomy. J Urol 1983; 129: 1145–1156.

    Article  Google Scholar 

  2. Gleason DF . Classification of prostatic carcinomas. Cancer Chemother Rep 1966; 50: 125–128.

    CAS  PubMed  Google Scholar 

  3. Grayhack JT, Assimos DG . Prognostic significance of tumor grade and stage in the patient with carcinoma of the prostate. Prostate 1983; 4: 13–31.

    Article  CAS  PubMed  Google Scholar 

  4. Epstein JL, Partin AW, Sauvageot J, Walsh PC . Prediction of progression following radical prostatectomy. A multivariate analysis of 721 men with long-term follow-up. Am J Surg Pathol 1996; 20: 286–292.

    Article  CAS  PubMed  Google Scholar 

  5. Oefelein MG, Colangelo L, Grayhack J, McVary KT . Survival after radical retropubic prostatectomy in men with clinically localized high grade carcinoma of the prostate. Cancer 1995; 76: 2523.

    Article  Google Scholar 

  6. Fritz IB, Burdzy BK, Setchell B, Blaschuk O . Ram rete testis fluid contains a protein (clusterin) which influences cell–cell interactions in vitro. Biol Reprod 1983; 28: 1173–1188.

    Article  CAS  PubMed  Google Scholar 

  7. de Silva HV et al. Apolipoprotein J: structure and tissue distribution. Biochemistry 1990; 29: 5380–5389.

    Article  CAS  PubMed  Google Scholar 

  8. Jenne DE, Tschopp J . Molecular structure and functional characterization of a human complement cytolytic inhibitor found in blood and seminal plasma: identity to sulfated glycoprotein-2, a constituent of rat testis fluid. Proc Natl Acad Sci USA 1989; 86: 7123–7127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Jenne DE, Tschopp J . Clusterin: the intriguing guises of a widely expressed glycoprotein. Trends Biochem Sci 1992; 17: 154–159.

    Article  CAS  PubMed  Google Scholar 

  10. Leger JG, Montpetit ML, Tenniswood MP . Characterization and cloning of androgen-repressed mRNAs from rat ventral prostate. Biochem Biophys Res Commun 1987; 147: 196–203.

    Article  CAS  PubMed  Google Scholar 

  11. Sylveste SR, Morales C, Oko R, Griswold MD . Localization of sulfated glycoprotein-2 (clusterin) on spermatozoa and in the reproductive tract of the male rat. Biol Reprod 1991; 31: 1087–1101.

    Article  Google Scholar 

  12. Sensibar JA et al. Prevention of cell death induced by tumor necrosis factor alpha in LNCaP cells by overexpression of sulfated glycoprotein-2 (clusterin). Cancer Res 1995; 55: 2431–2437.

    CAS  PubMed  Google Scholar 

  13. Sintich S et al. Cytotoxic sensitivity to tumor necrosis factor-α in prostate cancer cells is regulated by extracellular levels of SGP-2 (clusterin). Prostate 1999; 39: 87–93.

    Article  CAS  PubMed  Google Scholar 

  14. Steinberg J et al. Intracellular levels of SGP-2 (Clusterin) correlate with tumor grade in prostate cancer. Clin Cancer Res 1997; 3: 1707–1711.

    CAS  PubMed  Google Scholar 

  15. Miyake H, Nelson C, Rennie PS, Gleave ME . Testosterone-repressed prostate message-2 is an antiapoptotic gene involved in progression to androgen-independence in prostate cancer. Cancer Res 2000; 60: 170–176.

    CAS  PubMed  Google Scholar 

  16. Miyake H, Hara I, Kamidono S, Gleave ME . Synergistic chemosensitivity and inhibition of tumor growth and metastasis by the antisense oligodeoxynucleotide targeting clusterin gene in a human bladder cancer model. Clin Cancer Res 2001; 7: 4245–4252.

    CAS  PubMed  Google Scholar 

  17. Zellweger T et al. Antitumor activity of antisense clusterin oligonucleotides is improved in vitro and in vivo by incorporation of 2′-O-(2-methoxy)ethyl chemistry. J Pharmacol. Exp Ther 2001; 298: 934–940.

    CAS  PubMed  Google Scholar 

  18. Zellweger T et al. Enhanced radiation sensitivity in prostate cancer by inhibition of the cell survival protein clusterin. Clin Cancer Res 2002; 8: 3276–3284.

    CAS  PubMed  Google Scholar 

  19. Rosner B . Fundamentals of Biostatistics, 5th edn. Duxbury Press: Pacific Grove, CA 2000.

    Google Scholar 

  20. Winer BJ, Brown DR, Michels KM . Statistical Principles in Experimental Design, 3rd edn. McGraw-Hill: New York, NY 1991; pp 158, 358.

  21. Sensibar JA et al. Prostatic ductal system in rats: regional variation in localization of an androgen-repressed gene product, sulfated glycoprotein-2. Endocrinology 1991; 128: 2091–2102.

    Article  CAS  PubMed  Google Scholar 

  22. Bettuzzi S et al. Clusterin gene expression is down-regulated in transformed epithelial cells but up-regulated in fibroblasts from prostate cancer. J Urol 2003; 169: 159 (Abstract 617).

    Google Scholar 

  23. Ignatoff JM et al. Prostate specific antigen reverse transcriptase-polymerase chain reaction assay in preoperative staging of prostate cancer. J Urol 1997; 158: 1870–1874.

    Article  CAS  PubMed  Google Scholar 

  24. Oefelein MG et al. Molecular detection of prostate epithelial cells from the surgical field and peripheral circulation during radical prostatectomy. J Urol 1995; 155: 238–242.

    Article  Google Scholar 

  25. Oefelein MG et al. Clinical follow-up after radical retropubic prostatectomy. J Urol 1999; 162: 293–306.

    Article  Google Scholar 

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Acknowledgements

This study was supported in part by NIH Grants CA80963 and CA90386. We thank for the constructive comments of Dr Beatrice Knudson of the Fred Hutchinson Cancer Research Center.

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Correspondence to C Lee.

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An abstract of this report was presented at the NCI sponsored prostate cancer SPORE workshop, Westfield Conference Center, Chantilly, Virginia, July 14–16, 2002.

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Pins, M., Fiadjoe, J., Korley, F. et al. Clusterin as a possible predictor for biochemical recurrence of prostate cancer following radical prostatectomy with intermediate Gleason scores: a preliminary report. Prostate Cancer Prostatic Dis 7, 243–248 (2004). https://doi.org/10.1038/sj.pcan.4500722

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