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Article

Loss of CDKN1B/p27Kip1 expression is associated with ERG fusion‑negative prostate cancer, but is unrelated to patient prognosis

  • Authors:
    • Hüseyin Sirma
    • Margarethe Broemel
    • Laura Stumm
    • Tina Tsourlakis
    • Stefan Steurer
    • Pierre Tennstedt
    • Georg Salomon
    • Uwe Michl
    • Alexander Haese
    • Ronald Simon
    • Guido Sauter
    • Thorsten Schlomm
    • Sarah Minner
  • View Affiliations / Copyright

    Affiliations: Institute of Pathology, Prostate Cancer Center and Section for Translational Prostate Cancer Research at Clinic of Urology, University Medical Center Hamburg‑Eppendorf, Hamburg D‑20246, Germany, Martini Clinic, Prostate Cancer Center and Section for Translational Prostate Cancer Research at Clinic of Urology, University Medical Center Hamburg‑Eppendorf, Hamburg D‑20246, Germany
  • Pages: 1245-1252
    |
    Published online on: September 4, 2013
       https://doi.org/10.3892/ol.2013.1563
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Abstract

The cyclin‑dependent kinase inhibitor p27Kip1 has been suggested as a prognostic marker in prostate cancer. The aim of this study was to determine the clinical and prognostic role of p27 expression in hormone‑naive prostate cancers. A tissue microarray containing samples from 4,699 prostate cancers with attached pathological, clinical follow‑up and molecular data was analyzed for nuclear p27 expression by immunohistochemistry. p27 staining was negative in 18.6%, weak in 33.5%, moderate in 28.4% and strong in 19.5% of 3,701 interpretable cancer spots. Loss of p27 immunostaining was linked to tumors of low Gleason grade (P<0.0001) and ERG fusion‑negative cancers (P<0.0001). p27 levels were not associated with other parameters, including tumor stage, nodal stage, preoperative prostate‑specific antigen (PSA) levels, surgical margin status and cell proliferation (as measured by the Ki67 labeling index). p27 expression was also unrelated to clinical outcome in all cancers, as well as in the subsets of ERG fusion‑positive and ‑negative cancers. Overall, the present data demonstrated that elevated p27 expression was often unrelated to prostate cancer phenotype. Furthermore, the lack of an effect of the p27 protein levels on PSA recurrence following radical prostatectomy indicated that factors other than p27 expression are likely to be the major determinants of prostate cancer recurrence. However, a subset of ERG‑negative, low‑grade tumors was frequently characterized by loss of p27, suggesting a role of this alteration for the development of these tumors.
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1 

Cooperberg MR, Cowan J, Broering JM and Carroll PR: High-risk prostate cancer in the United States, 1990–2007. World J Urol. 26:211–218. 2008.

2 

Samaratunga H and Epstein JI: What is the molecular pathology of low-risk prostate cancer? World J Urol. 26:431–436. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Rubin MA, Maher CA and Chinnaiyan AM: Common gene rearrangements in prostate cancer. J Clin Oncol. 29:3659–3668. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Tsihlias J, Kapusta L and Slingerland J: The prognostic significance of altered cyclin-dependent kinase inhibitors in human cancer. Annu Rev Med. 50:401–423. 1999. View Article : Google Scholar : PubMed/NCBI

5 

Wander SA, Zhao D and Slingerland JM: p27: a barometer of signaling deregulation and potential predictor of response to targeted therapies. Clin Cancer Res. 17:12–18. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Swanson GP and Quinn D: Using molecular markers to help predict who will fail after radical prostatectomy. Prostate Cancer. 2011:2901602011. View Article : Google Scholar : PubMed/NCBI

7 

Tsihlias J, Kapusta LR, DeBoer G, et al: Loss of cyclin-dependent kinase inhibitor p27Kip1 is a novel prognostic factor in localized human prostate adenocarcinoma. Cancer Res. 58:542–548. 1998.

8 

Vis AN, Noordzij MA, Fitoz K, Wildhagen MF, Schröder FH and van der Kwast TH: Prognostic value of cell cycle proteins p27(kip1) and MIB-1, and the cell adhesion protein CD44s in surgically treated patients with prostate cancer. J Urol. 164:2156–2161. 2000. View Article : Google Scholar : PubMed/NCBI

9 

Vis AN, van Rhijn BW, Noordzij MA, Schröder FH and van der Kwast TH: Value of tissue markers p27(kip1), MIB-1, and CD44s for the pre-operative prediction of tumour features in screen-detected prostate cancer. J Pathol. 197:148–154. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Yang RM, Naitoh J, Murphy M, et al: Low p27 expression predicts poor disease-free survival in patients with prostate cancer. J Urol. 159:941–945. 1998. View Article : Google Scholar : PubMed/NCBI

11 

Revelos K, Petraki C, Gregorakis A, et al: p27(kip1) and Ki-67 (MIB1) immunohistochemical expression in radical prostatectomy specimens of patients with clinically localized prostate cancer. In Vivo. 19:911–920. 2005.

12 

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

13 

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

14 

Kuczyk MA, Bokemeyer C, Hartmann J, et al: Predictive value of altered p27Kip1 and p21WAF/Cip1 protein expression for the clinical prognosis of patients with localized prostate cancer. Oncol Rep. 8:1401–1407. 2001.PubMed/NCBI

15 

Cordon-Cardo C, Koff A, Drobnjak M, et al: Distinct altered patterns of p27KIP1 gene expression in benign prostatic hyperplasia and prostatic carcinoma. J Natl Cancer Inst. 90:1284–1291. 1998. View Article : Google Scholar : PubMed/NCBI

16 

Cote RJ, Shi Y, Groshen S, et al: Association of p27Kip1 levels with recurrence and survival in patients with stage C prostate carcinoma. J Natl Cancer Inst. 90:916–920. 1998. View Article : Google Scholar : PubMed/NCBI

17 

Cheville JC, Lloyd RV, Sebo TJ, et al: Expression of p27kip1 in prostatic adenocarcinoma. Mod Pathol. 11:324–328. 1998.PubMed/NCBI

18 

Erdamar S, Yang G, Harper JW, et al: Levels of expression of p27KIP1 protein in human prostate and prostate cancer: an immunohistochemical analysis. Mod Pathol. 12:751–755. 1999.PubMed/NCBI

19 

Halvorsen OJ, Haukaas SA and Akslen LA: Combined loss of PTEN and p27 expression is associated with tumor cell proliferation by Ki-67 and increased risk of recurrent disease in localized prostate cancer. Clin Cancer Res. 9:1474–1479. 2003.PubMed/NCBI

20 

Nassif AE and Tambara Filho R: Immunohistochemistry expression of tumor markers CD34 and P27 as a prognostic factor of clinically localized prostate adenocarcinoma after radical prostatectomy. Rev Col Bras Cir. 37:338–344. 2010.

21 

Vlachostergios PJ, Karasavvidou F, Kakkas G, et al: Lack of prognostic significance of p16 and p27 after radical prostatectomy in hormone-naïve prostate cancer. J Negat Results Biomed. 11:22012.PubMed/NCBI

22 

Wu TT, Wang JS, Jiaan BP, et al: Role of p21(WAF1) and p27(KIP1) in predicting biochemical recurrence for organ-confined prostate adenocarcinoma. J Chin Med Assoc. 70:11–15. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Minner S, Enodien M, Sirma H, et al: ERG status is unrelated to PSA recurrence in radically operated prostate cancer in the absence of antihormonal therapy. Clin Cancer Res. 17:5878–5888. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Minner S, Jessen B, Stiedenroth L, et al: Low level HER2 overexpression is associated with rapid tumor cell proliferation and poor prognosis in prostate cancer. Clin Cancer Res. 16:1553–1560. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Thomas GV, Schrage MI, Rosenfelt L, et al: Preoperative prostate needle biopsy p27 correlates with subsequent radical prostatectomy p27, Gleason grade and pathological stage. J Urol. 164:1987–1991. 2000. View Article : Google Scholar

26 

Mukai M, Dong Q, Hardy MP, Kiyokawa H, Peterson RE and Cooke PS: Altered prostatic epithelial proliferation and apoptosis, prostatic development, and serum testosterone in mice lacking cyclin-dependent kinase inhibitors. Biol Reprod. 73:951–958. 2005. View Article : Google Scholar

27 

Shen MM and Abate-Shen C: Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev. 24:1967–2000. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Sreenath TL, Dobi A, Petrovics G and Srivastava S: Oncogenic activation of ERG: A predominant mechanism in prostate cancer. J Carcinog. 10:372011. View Article : Google Scholar : PubMed/NCBI

29 

Clark JP and Cooper CS: ETS gene fusions in prostate cancer. Nat Rev Urol. 6:429–439. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Setlur SR, Mertz KD, Hoshida Y, et al: Estrogen-dependent signaling in a molecularly distinct subclass of aggressive prostate cancer. J Natl Cancer Inst. 100:815–825. 2008. View Article : Google Scholar : PubMed/NCBI

31 

Jhavar S, Brewer D, Edwards S, et al: Integration of ERG gene mapping and gene-expression profiling identifies distinct categories of human prostate cancer. BJU Int. 103:1256–1269. 2009. View Article : Google Scholar

32 

Brase JC, Johannes M, Mannsperger H, et al: TMPRSS2-ERG -specific transcriptional modulation is associated with prostate cancer biomarkers and TGF-β signaling. BMC Cancer. 11:5072011.PubMed/NCBI

33 

Taylor BS, Schultz N, Hieronymus H, et al: Integrative genomic profiling of human prostate cancer. Cancer Cell. 18:11–22. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Müller J, Ehlers A, Burkhardt L, et al: Loss of p(Ser2448)-mTOR expression is linked to adverse prognosis and tumor progression in ERG-fusion-positive cancers. Int J Cancer. 132:1333–1340. 2012.PubMed/NCBI

35 

Minner S, Wittmer C, Graefen M, et al: High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate. 71:281–288. 2011. View Article : Google Scholar : PubMed/NCBI

36 

Tennstedt P, Köster P, Bruchmann A, et al: The impact of the number of cores on tissue microarray studies investigating prostate cancer biomarkers. Int J Oncol. 40:261–268. 2012.

37 

El Gammal AT, Bruchmann M, Zustin J, et al: Chromosome 8p deletions and 8q gains are associated with tumor progression and poor prognosis in prostate cancer. Clin Cancer Res. 16:56–64. 2010.PubMed/NCBI

38 

Schlomm T, Iwers L, Kirstein P, et al: Clinical significance of p53 alterations in surgically treated prostate cancers. Mod Pathol. 21:1371–1378. 2008. View Article : Google Scholar : PubMed/NCBI

39 

Schlomm T, Kirstein P, Iwers L, et al: Clinical significance of epidermal growth factor receptor protein overexpression and gene copy number gains in prostate cancer. Clin Cancer Res. 13:6579–6584. 2007. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Sirma H, Broemel M, Stumm L, Tsourlakis T, Steurer S, Tennstedt P, Salomon G, Michl U, Haese A, Simon R, Simon R, et al: Loss of CDKN1B/p27Kip1 expression is associated with ERG fusion‑negative prostate cancer, but is unrelated to patient prognosis. Oncol Lett 6: 1245-1252, 2013.
APA
Sirma, H., Broemel, M., Stumm, L., Tsourlakis, T., Steurer, S., Tennstedt, P. ... Minner, S. (2013). Loss of CDKN1B/p27Kip1 expression is associated with ERG fusion‑negative prostate cancer, but is unrelated to patient prognosis. Oncology Letters, 6, 1245-1252. https://doi.org/10.3892/ol.2013.1563
MLA
Sirma, H., Broemel, M., Stumm, L., Tsourlakis, T., Steurer, S., Tennstedt, P., Salomon, G., Michl, U., Haese, A., Simon, R., Sauter, G., Schlomm, T., Minner, S."Loss of CDKN1B/p27Kip1 expression is associated with ERG fusion‑negative prostate cancer, but is unrelated to patient prognosis". Oncology Letters 6.5 (2013): 1245-1252.
Chicago
Sirma, H., Broemel, M., Stumm, L., Tsourlakis, T., Steurer, S., Tennstedt, P., Salomon, G., Michl, U., Haese, A., Simon, R., Sauter, G., Schlomm, T., Minner, S."Loss of CDKN1B/p27Kip1 expression is associated with ERG fusion‑negative prostate cancer, but is unrelated to patient prognosis". Oncology Letters 6, no. 5 (2013): 1245-1252. https://doi.org/10.3892/ol.2013.1563
Copy and paste a formatted citation
x
Spandidos Publications style
Sirma H, Broemel M, Stumm L, Tsourlakis T, Steurer S, Tennstedt P, Salomon G, Michl U, Haese A, Simon R, Simon R, et al: Loss of CDKN1B/p27Kip1 expression is associated with ERG fusion‑negative prostate cancer, but is unrelated to patient prognosis. Oncol Lett 6: 1245-1252, 2013.
APA
Sirma, H., Broemel, M., Stumm, L., Tsourlakis, T., Steurer, S., Tennstedt, P. ... Minner, S. (2013). Loss of CDKN1B/p27Kip1 expression is associated with ERG fusion‑negative prostate cancer, but is unrelated to patient prognosis. Oncology Letters, 6, 1245-1252. https://doi.org/10.3892/ol.2013.1563
MLA
Sirma, H., Broemel, M., Stumm, L., Tsourlakis, T., Steurer, S., Tennstedt, P., Salomon, G., Michl, U., Haese, A., Simon, R., Sauter, G., Schlomm, T., Minner, S."Loss of CDKN1B/p27Kip1 expression is associated with ERG fusion‑negative prostate cancer, but is unrelated to patient prognosis". Oncology Letters 6.5 (2013): 1245-1252.
Chicago
Sirma, H., Broemel, M., Stumm, L., Tsourlakis, T., Steurer, S., Tennstedt, P., Salomon, G., Michl, U., Haese, A., Simon, R., Sauter, G., Schlomm, T., Minner, S."Loss of CDKN1B/p27Kip1 expression is associated with ERG fusion‑negative prostate cancer, but is unrelated to patient prognosis". Oncology Letters 6, no. 5 (2013): 1245-1252. https://doi.org/10.3892/ol.2013.1563
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