Skip to main content
SpringerLink
Log in

Immunohistochemical detection of retinoic acid receptorα in prostate carcinoma: Correlation with proliferative activity and tumor grade

  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Background: The use of retinoids as differentiation therapy is a novel approach to prostate cancer. Retinoids act via their own nuclear receptors, RARs and RXRs, modulating gene activity, cell growth and differentiation. This study provides new data on the content and cellular distribution of RARα protein in prostate cancer specimens, in correlation to tumor grade and proliferative activity. Material and methods: A total of 84 cases of primary prostate carcinoma, divided into 3 subgroups according to tumor grade, were immunohistochemically evaluated for retinoic acid receptor-α (RARα) and Ki67 using the streptavidin/peroxidase method on formalin fixed, paraffin embedded tissues. Results: RARα positivity was detected in all cases of prostatic carcinoma, with a more profound expression in well differentiated cancers. A statistically significant correlation between RARα staining and tumor grade was found (ANOVA, p < 0.031). Ki67 immunoreactivity was present in 35.7% of cases, but no correlation with tumor grade was found. When RARα staining was correlated with Ki67 positivity, a statistically significant correlation was present (unpaired t-test, p < 0.003). Conclusions: These findings indicate that RARα expression is correlated to some extent with tumor grade and its presence is more profound in highly proliferative tumors. Further studies are needed to establish the possible clinical value of the immunohistochemical evaluation of RARα content in tumor specimens.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics. CA Cancer J Clin 1996; 46: 5–27.

    PubMed  CAS  Google Scholar 

  2. Dijkman GA, Debruyne FM. Epidemiology of prostate cancer. Eur Urol 1996; 30: 281.

    PubMed  CAS  Google Scholar 

  3. Labrie F, Cusan L, Gomez JL, Diamond P, Candas B. Combination of screening and preoperative endocrine therapy: the potential for an important decrease in prostate cancer mortality. J Clin Endocr Metab 1996; 80: 2002–2013.

    Google Scholar 

  4. De Luka LM, Darwiche N, Jones CS, Scita G. Retinoids in differentiation and neoplasia. Scientific American; July/Aug 28-37 1995.

  5. Van der Leede BM, Geertzema J, Vroom TM et al. Immunohistochemical analysis of retinoic acid receptor-α in human breast tumors. Am J Pathol 1996; 148: 1905–1914.

    PubMed  CAS  Google Scholar 

  6. Katsetos CD, Stadnicka I, Boyd JC et al. Cellular distribution of retinoic acid receptor-α protein in serous adenocarcinomas of ovarian, tubal and peritoneal origin. Am J Pathol 1998; 153: 469–480.

    PubMed  CAS  Google Scholar 

  7. Prayson RA. Cyclin D1 and MIB1 immunohistochemistry in ependymomas. Am J Clin Pathol 1998; 110: 629–634.

    PubMed  CAS  Google Scholar 

  8. Lai R, Medeiros LJ, Wilson CS et al. Expression of the cell-cycle-related proteins E2F-1, p53, mdm-2, p21waf-1 and Ki67 in multiple myeloma: correlation with cyclin D1 immunoreactivity. Mod Pathol 1998; 11(7): 642–647.

    PubMed  CAS  Google Scholar 

  9. Renshaw AA, Loughlin KR, Dutta A. Cyclin A and MIB1 (Ki67) as markers of proliferative activity in primary renal neoplasms. Mod Pathol 1998; 11(10): 963–966.

    PubMed  CAS  Google Scholar 

  10. Gleason DF. Classification of prostatic carcinomas. Cancer Chemother Rep 1996; 50: 125–136.

    Google Scholar 

  11. Olapade-Olaopa E, Mackay EH. Variability of immunohistochemical reactivity on stored paraffin slides. J Clin Pathol 1998(letter); 51: 943.

    Article  PubMed  CAS  Google Scholar 

  12. Bertheau P, Cazals-Hatem D, Meignin V et al. Variability of immunohistochemical reactivity on stored paraffin slides. J Clin Pathol 1998; 51: 370–374.

    PubMed  CAS  Google Scholar 

  13. Loda M, Fogt F, French FS et al. Androgen receptor immunohistochemistry on paraffin-embedded tissue. Mod Pathol 1994; 7(3): 388–391.

    PubMed  CAS  Google Scholar 

  14. Gerdes J. Ki67 and other proliferation markers useful for immunohistological diagnosis and prognostic evaluations in human malignancies. Sem Cancer Biol 1990; 1: 199.

    CAS  Google Scholar 

  15. Scott RJ, Hall PA, Haldane JS et al. A comparison of immunohistochemical markers of cell proliferation with experimentally determined growth fraction. J Pathol 1991; 165: 173–177.

    PubMed  CAS  Google Scholar 

  16. Quinn CM. Wright NA. The clinical assessment of proliferation and growth in human tumors: evaluation of methods and applications as prognostic variables. J Pathol 1990; 160: 93.

    PubMed  CAS  Google Scholar 

  17. Bubendorf L, Sauter G, Moch H et al. Ki67 labelling index: an independent predictor of progression in prostate cancer treated by radical prostatectomy. J Pathol 1996; 178: 437.

    PubMed  CAS  Google Scholar 

  18. Bettencourt MC, Bauer JJ, Sesterhenn IA, Mostofi FK, McLeod DG, Moul JW. Ki67 expression is a prognostic marker of prostate cancer recurrence after radical prostatectomy. J Urol 1996; 156: 1064.

    PubMed  CAS  Google Scholar 

  19. Stattin P, Damber JE, Karlberg L, Bergh A. Cell proliferation assessed by Ki67 immunoreactivity on formalin fixed tissues is a predictive factor for survival in prostate cancer. J Urol 1997; 157: 219–222.

    PubMed  CAS  Google Scholar 

  20. Vartanian RK, Weidner N. Endothelial cell proliferation in prostatic carcinoma and prostatic hyperplasia: correlation with GleasonŠs score, microvessel density and epithelial cell proliferation. Lab Invest 1995; 73(6): 844–850.

    PubMed  CAS  Google Scholar 

  21. Chorny JA, Kruse CA, Kleinschmidt-DeMasters BK et al. immunohistochemical study of the retinoic acid receptor α in normal versus neoplastic human tissues. Appl Immunohistochem 1995; 3: 64–71.

    Google Scholar 

  22. Van der Leede BM, Folkers GE, van den Brink CE, van der Saag PT, van der Burg B. Retinoic acid receptor α 1 isoform is induced by estradiol and confers retinoic acid sensitivity in human breast cancer cells. Mol Cell Endocrinol 1995; 109: 77–86.

    PubMed  CAS  Google Scholar 

  23. Sheikh MS, Shao Z-M, Li X-S et al. Retinoid resistant estrogen receptor negative human breast carcinoma cells transferred with retinoic acid receptor α acquire sensitivity to growth inhibition by retinoids. J Biol Chem 1994; 269: 21440–21447.

    PubMed  CAS  Google Scholar 

  24. Trump DL. Retinoids in bladder, testis and prostate cancer: epidemiologic, pre-clinical and clinical observations. Leukemia 8 Suppl 1994; 3: S50–54.

    Google Scholar 

  25. Liang JY, Fontana JA, Rao JN. Synthetic retinoid CD437 induces S-phase arrest and apoptosis in human prostate cancer cells LNCaP and PC-3. Prostate 1999; 38: 228–236.

    PubMed  CAS  Google Scholar 

  26. Lu XP, Fanjul A, Picerd N, Shroot B, Pfahl M. A selective retinoid with high activity against an androgen-resistant prostate cancer cell type. Int J Cancer 1999; 80: 272–278.

    PubMed  CAS  Google Scholar 

  27. Zhuang SH, Burstein KL. Antiproliferative effect of la, 25-dihydroxyvitamin D3 in human prostate cancer cell line LNCaP involves reduction of cyclin-dependent kinase 2 activity and persistent G1 accumulation. Endocrinology 1998; 139(3): 1197–1207.

    PubMed  CAS  Google Scholar 

  28. Sun SY, Yue P, Lotan R. Induction of apoptosis by N-(4-Hydroxyphenyl)retinamide and its association with reactive oxygen species, nuclear retinoic acid receptors and apoptosisrelated genes in human prostate carinoma cells. Mol Pharmacol 1999: 59(3): 521–524.

    Google Scholar 

  29. Shen JC, Wang TT, Chang S, Husrsting SD. Mechanistic studies of the effects of the retinoid N-(4-hudroxyphenyl) retinamide on prostate cancer cell growth and apoptosis. Mol Carcinog 1999; 24(3): 160–168.

    PubMed  CAS  Google Scholar 

  30. Debruyne DL, DePorre P, Bruynseels J. Early clinical experience with liarozole (LiazalTM) in patients with progressive prostate cancer. Eur J Cancer 1998; 34: 469–475.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, School of Medicine, University of Patras, Patras, Greece

    K. Gyftopoulos, P. Perimenis & G.A. Barbalias

  2. Department of Anatomy, School of Medicine, University of Patras, Patras, Greece

    G. Sotiropoulou-Bonikou & I. Varakis

  3. Department of Medical Physics, School of Medicine, University of Patras, Patras, Greece

    G. Sakellaropoulos

Authors
  1. K. Gyftopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Perimenis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Sotiropoulou-Bonikou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Sakellaropoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I. Varakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G.A. Barbalias
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gyftopoulos, K., Perimenis, P., Sotiropoulou-Bonikou, G. et al. Immunohistochemical detection of retinoic acid receptorα in prostate carcinoma: Correlation with proliferative activity and tumor grade. Int Urol Nephrol 32, 263–269 (2000). https://doi.org/10.1023/A:1007126332651

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1007126332651

Search

Navigation