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Expression of p21waf1/cip1, p27kip1, p63 and Androgen Receptor in Low and High Gleason Score Prostate Cancer

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Pathology & Oncology Research

Abstract

The aim of this study was to investigate the expression of p21waf1/cip1, p27kip1, p63 and androgen receptor proteins in relation to serum prostate specific antigen levels in low and high Gleason score prostate cancers. Biopsies of patients suffering from prostate adenocarcinoma of low (3 + 3 to 3 + 4) and high (5 + 4 to 5 + 5) Gleason scores (13 cases each group) were immunostained for positive regulators of cell cycle control (p21waf1/cip1 and p27kip1), and essential markers of normal prostate gland ontogeny (p63) and growth (androgen receptor) to find differentially expressed markers of malignant progression. Serum prostate specific antigen levels were also monitored at the time of biopsy and following anti-androgen therapy. All cases except one in each group were androgen receptor positive. P63 and p21waf1/cip1 proteins detected in normal basal cell nuclei were lost in all but one studied tumors respectively. P27kip1 protein, however, was detected in all low Gleason score prostate cancers, but it was found in only 7/13 high score cases. Prostate specific antigen levels, either pre- or post-treatment, did not show strict correlation with the p27kip1 results. The low to high grade dedifferentiation of prostate adenocarcinoma is accompanied with the down-regulation of p27kip1 protein, which may be an important molecular sign of the lost cell cycle control.

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Abbreviations

AR:

androgen receptors

H&E:

Haematoxylin–eosin

PSA:

prostate specific antigen

CAB:

complete androgen blockade

References

  1. Isaacs JT, Lundmo PI, Berges R, Martikainen P, Kyprianou N, English HF (1992) Androgen regulation of programmed death of normal and malignant prostatic cells. J Androl 13:457–464

    CAS  PubMed  Google Scholar 

  2. Eder IE, Culig Z, Putz T, Nessler-Menardi C, Bartsch G, Klocker H (2001) Molecular biology of the androgen receptor: from molecular understanding to the clinic. Eur Urol 40:241–251

    Article  CAS  PubMed  Google Scholar 

  3. Stamey TA, Warrington JA, Caldwell MC et al (2001) Molecular genetic profiling of Gleason grade 4/5 prostate cancers compared to benign prostatic hyperplasia. J Urol 166:2171–2177

    Article  CAS  PubMed  Google Scholar 

  4. Porkka KP, Visakorpi T (2001) Detection of differentially expressed genes in prostate cancer by combining suppression subtractive hybridization and cDNA library assay. J Pathol 193:73–79

    Article  CAS  PubMed  Google Scholar 

  5. Meehan KL, Holland JW, Dawkins HJ (2002) Proteomic analysis of normal and malignant prostate tissue to identify novel proteins lost in cancer. Prostate 50:54–63

    Article  CAS  PubMed  Google Scholar 

  6. Baretton GB, Klenk U, Diebold J, Schmeller N, Lohrs U (1999) Proliferation- and apoptosis-associated factors in advanced prostatic carcinomas before and after androgen deprivation therapy: prognostic significance of p21/WAF1/CIP1 expression. Br J Cancer 80:546–555

    Article  CAS  PubMed  Google Scholar 

  7. Eder IE, Bektic J, Haag P, Bartsch G, Klocker H (2004) Genes differentially expressed in prostate cancer. BJU Int 93:1151–1155

    Article  CAS  PubMed  Google Scholar 

  8. Szende B, Romics I, Minik K, Szabó J, Torda I, Lovász S, Tóth L, Bély M, Kerényi T, Bartók K, Végh A (2001) Repeated biopsies in evaluation of therapeutic effects in prostate carcinoma. Prostate 49:93–100

    Article  CAS  PubMed  Google Scholar 

  9. Waltregny D, Leav I, Signoretti S, Soung P, Lin D, Merk F, Adams JY, Bhattecharya N, Cirenei N, Loda M (2001) Androgen-driven prostate epithelial cell proliferation and differentiation in vivo involve the regulation of p27. Mol Endocrinol 15:765–782

    Article  CAS  PubMed  Google Scholar 

  10. Koffer L, Roshong S, Park IK, Cesen-Cummings K, Thopson DR, Dwyer-Nield LD, Rice P, Mamay C, Malkinson AM, Ruch RJ (2000) Growth inhibition in G1 and altered expression of cyclin D1 and p27kip1 after forced connexin expression in lung and liver carcinoma cells. J Cell Biochem 79:347–354

    Article  Google Scholar 

  11. Zhang Y-W, Morite I, Ikeda M, Ma K-W, Murota S (2001) Connexin43 suppresses proliferation of osteosarcoma U2OS cells through post-transcriptional regulation of p27. Oncogene 20:4138–4149

    Article  CAS  PubMed  Google Scholar 

  12. Gorbe A, Becker DL, Dux L, Stelkovics E, Krenacs L, Bagdi E, Krenacs T (2005) Transient upregulation of connenxin43 gap junctions and synchronized cell cycle control precede myoblast fusion in regenerating skeletal muscle in vivo. Histochem Cell Biol 123:573–583

    Article  CAS  PubMed  Google Scholar 

  13. Lawlor MA, Rotwein P (2000) Coordinate control of muscle cell survival by distinct insulin-like growth factor activated signaling pathways. J Cell Biol 151:1131–1140

    Article  CAS  PubMed  Google Scholar 

  14. Ostrovsky O, Bengal E (2003) The mitogen-activated protein kinase cascade promotes myoblast cell survival by stabilizing the cyclin-dependent kinase inhibitor, p21WAF1 protein. J Biol Chem 278:21221–21231

    Article  CAS  PubMed  Google Scholar 

  15. Fizazi K, Martizez LA, Sikes CR, Johnston DA, Stephens LC, McDonnell TJ, Logothetis CJ, Trapman J, Pisters LL, Ordonez NG, Troncoso P, Navone NM (2002) The association of p21 (WAF-1/CIP1) with progression to androgen-independent prostate cancer. Clin Cancer Res 8:775–781

    CAS  PubMed  Google Scholar 

  16. Signoretti S, Waltregny D, Dilks J, Isaac B, Lin D, Garraway L, Yang A, Montironi R, McKeon F, Loda M (2000) P63 is a prostate basal cell marker and is required for prostate development. Am J Pathol 157:1769–1775

    CAS  PubMed  Google Scholar 

  17. Ronison IB (2003) Tumor cell senescence in cancer treatment. Cancer Res 63:2705–2715

    Google Scholar 

  18. Di Como CJ, Urist MJ, Babayan I, Drobnjak M, Hedvat CV, Teruya-Feldstein J, Pohar K, Hoos A, Cordon-Cardo C (2002) P63 expression profiles in human normal and tumor tissues. Clin Can Res 8:494–501

    Google Scholar 

  19. Cordon-Cardo G, Koff A, Drobnjak M, Caodieci P, Osman I, Millard SS (1998) Distinct altered patterns of 27kip1 gene expression in benign prostate hyperplasia and prostatic carcinoma. J Natl Cancer Inst 90:1284–1291

    Article  CAS  PubMed  Google Scholar 

  20. Guo Y, Sklar GN, Borkowski A, Kyprianou N (1997) Loss of the cyclin dependent kinase inhibitor p27(Kip1) protein in human prostate cancers correlates with tumor grade. Clin Cancer Res 3:2269–2274

    CAS  PubMed  Google Scholar 

  21. Kuczyk M, Machtens S, Hradil K et al (1999) Predictive value of p27Kip1 protein expression for the recurrence-free and long-term survival of prostate cancer patients. Br J Cancer 81:1052–1058

    Article  CAS  PubMed  Google Scholar 

  22. Doganavsargil B, Simsir A, Boyacioglu H, Cal C, Hekimgil M (2006) A comparison of p21 and p27 immunoexpression in benign glands, prostatic intraepithelial neoplasia and prostate adenocarcinoma. BJU Int 97:644–648

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Béla Szende.

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Romics, I., Bánfi, G., Székely, E. et al. Expression of p21waf1/cip1, p27kip1, p63 and Androgen Receptor in Low and High Gleason Score Prostate Cancer. Pathol. Oncol. Res. 14, 307–311 (2008). https://doi.org/10.1007/s12253-008-9042-z

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  • DOI: https://doi.org/10.1007/s12253-008-9042-z

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