Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular and Clinical Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9450 Online ISSN: 2049-9469
Journal Cover
March-April 2013 Volume 1 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-April 2013 Volume 1 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

The prognostic significance of loss of the androgen receptor and neuroendocrine differentiation in prostate biopsy specimens among castration-resistant prostate cancer patients

  • Authors:
    • Akira Komiya
    • Kenji Yasuda
    • Akihiko Watanabe
    • Yasuyoshi Fujiuchi
    • Toyonori Tsuzuki
    • Hideki Fuse
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, Japan, Department of Pathology, Nagoya Daini Red Cross Hospital, Nagoya 466-8650, Japan
  • Pages: 257-262
    |
    Published online on: January 14, 2013
       https://doi.org/10.3892/mco.2013.69
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Prostate cancer (PCa) is a leading cause of mortality, and despite good response to androgen ablation this response is eventually lost. In the present study, androgen receptor (AR) expression and neuroendocrine differentiation (NED) were evaluated in hormone-sensitive (HSPC) and castration-resistant prostate cancers (CRPC). Prostate tissues were obtained from 20 HSPC patients at diagnosis and 28 CRPC patients at castration‑resistant progression. AR, chromogranin A (CGA) and neuron-specific enolase (NSE) were evaluated by immunohistochemical staining (IHS) in representative positive cores for PCa. IHS intensity was graded as negative, 0; positive, 1+ and strongly positive, 2+. The proportion of the 1+ and 2+ areas in PCa cells was determined. PCa was considered to be in NED if ≥50% of the tumor cells were 1+ or 2+ for CGA or NSE. The observed IHS intensity (0/1+/2+) for AR, CGA and NSE was 0/4/16, 5/11/4 and 11/4/5 in HSPC patients and 9/3/16, 5/8/15 and 8/4/16 in CRPC patients, respectively. AR expression was positive in all the HSPC and 19/28 CRPC patients (P=0.0049). NED was observed in 9/20 HSPC and 20/28 CRPC patients (P=0.0649). NED was significantly associated with a negative AR expression in CRPC patients (P=0.0292). Multivariate analysis revealed that age, AR expression and strong NED were independent parameters for prognosis following castration-resistant progression. In conclusion, prostate biopsy following castration‑resistant progression was necessary. AR was lost in a subset of CRPC. NED was observed more frequently in CRPC vs. HSPC and was associated with a worse prognosis.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Suzuki H, Komiya A, Kamiya N, Imamoto T, Kawamura K, Miura J, Suzuki N, Nakatsu H, Hata A and Ichikawa T: Development of a nomogram to predict probability of positive initial prostate biopsy among Japanese patients. Urology. 67:131–136. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Yano M, Imamoto T, Suzuki H, Fukasawa S, Kojima S, Komiya A, Naya Y and Ichikawa T: The clinical potential of pretreatment serum testosterone level to improve the efficiency of prostate cancer screening. Eur Urol. 51:375–380. 2007. View Article : Google Scholar

3 

Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R, Petrylak D, Kantoff P, Basch E, Kelly WK, Figg WD, Small EJ, Beer TM, Wilding G, Martin A and Hussain M; Prostate Cancer Clinical Trials Working Group: Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 26:1148–1159. 2008. View Article : Google Scholar

4 

Scher HI, Buchanan G, Gerald W, Butler LM and Tilley WD: Targeting the androgen receptor: improving outcomes for castration-resistant prostate cancer. Endocr Relat Cancer. 11:459–476. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Attar RM, Takimoto CH and Gottardis MM: Castration-resistant prostate cancer: locking-up the molecular escape routes. Clin Cancer Res. 15:3251–3255. 2009. View Article : Google Scholar : PubMed/NCBI

6 

De Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Fléchon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM and Scher HI; COU-AA-301 Investigators: Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 364:1995–2005. 2011.

7 

Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME and Sawyers CL: Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 324:787–790. 2009. View Article : Google Scholar

8 

Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller MD, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Fléchon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L and de Bono JS; AFFIRM Investigators: Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 367:1187–1197. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Komiya A, Suzuki H, Imamoto T, Kamiya N, Nihei N, Naya Y, Ichikawa T and Fuse H: Neuroendocrine differentiation in the progression of prostate cancer. Int J Urol. 16:37–44. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Tanaka M, Suzuki Y, Takaoka K, Suzuki N, Murakami S, Matsuzaki O and Shimazaki J: Progression of prostate cancer to neuroendocrine cell tumor. Int J Urol. 8:431–436. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Grossmann ME, Huang H and Tindall DJ: Androgen receptor signaling in androgen-refractory prostate cancer. J Natl Cancer Inst. 93:1687–1697. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Zegarra-Moro OL, Schmidt LJ, Huang H and Tindall DJ: Disruption of androgen receptor function inhibits proliferation of androgen-refractory prostate cancer cells. Cancer Res. 62:1008–1013. 2002.PubMed/NCBI

13 

Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, Rosenfeld MG and Sawyers CL: Molecular determinants of resistance to antiandrogen therapy. Nat Med. 10:33–39. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Crook JM, O’Callaghan CJ, Duncan G, Dearnaley DP, Higano CS, Horwitz EM, Frymire E, Malone S, Chin J, Nabid A, Warde P, Corbett T, Angyalfi S, Goldenberg SL, Gospodarowicz MK, Saad F, Logue JP, Hall E, Schellhammer PF, Ding K and Klotz L: Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med. 367:895–903. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Nagata T, Shimada Y, Sekine S, Hori R, Matsui K, Okumura T, Sawada S, Fukuoka J and Tsukada K: Prognostic significance of NANOG and KLF4 for breast cancer. Breast Cancer. Apr 17–2012.(Epub ahead of print).

16 

Bonkhoff H and Berges R: From pathogenesis to prevention of castration resistant prostate cancer. Prostate. 70:100–112. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Hobisch A, Culig Z, Radmayr C, Bartsch G, Klocker H and Hittmair A: Distant metastases from prostatic carcinoma express androgen receptor protein. Cancer Res. 55:3068–3072. 1995.PubMed/NCBI

18 

Shah RB, Mehra R, Chinnaiyan AM, Shen R, Ghosh D, Zhou M, Macvicar GR, Varambally S, Harwood J, Bismar TA, Kim R, Rubin MA and Pienta KJ: Androgen-independent prostate cancer is a heterogeneous group of diseases: lessons from a rapid autopsy program. Cancer Res. 64:9209–9216. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Takeda H, Akakura K, Masai M, Akimoto S, Yatani R and Shimazaki J: Androgen receptor content of prostate carcinoma cells estimated by immunohistochemistry is related to prognosis of patients with stage D2 prostate carcinoma. Cancer. 77:934–940. 1996. View Article : Google Scholar : PubMed/NCBI

20 

Masai M, Sumiya H, Akimoto S, Yatani R, Chang CS, Liao SS and Shimazaki J: Immunohistochemical study of androgen receptor in benign hyperplastic and cancerous human prostates. Prostate. 17:293–300. 1990. View Article : Google Scholar : PubMed/NCBI

21 

Matei DV, Renne G, Pimentel M, Sandri MT, Zorzino L, Botteri E, De Cicco C, Musi G, Brescia A, Mazzoleni F, Tringali V, Detti S and de Cobelli O: Neuroendocrine differentiation in castration-resistant prostate cancer: a systematic diagnostic attempt. Clin Genitourin Cancer. 10:164–173. 2012. View Article : Google Scholar : PubMed/NCBI

22 

McWilliam LJ, Manson C and George NJ: Neuroendocrine differentiation and prognosis in prostatic adenocarcinoma. Br J Urol. 80:287–290. 1997. View Article : Google Scholar : PubMed/NCBI

23 

Kokubo H, Yamada Y, Nishio Y, Fukatsu H, Honda N, Nakagawa A, Saga S, Tsuzuki T and Hara K: Immunohistochemical study of chromogranin A in Stage D2 prostate cancer. Urology. 66:135–140. 2005. View Article : Google Scholar : PubMed/NCBI

24 

Kamiya N, Suzuki H, Kawamura K, Imamoto T, Naya Y, Tochigi N, Kakuta Y, Yamaguchi K, Ishikura H and Ichikawa T: Neuroendocrine differentiation in stage D2 prostate cancers. Int J Urol. 15:423–428. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Mucci NR, Akdas G, Manely S and Rubin MA: Neuroendocrine expression in metastatic prostate cancer: evaluation of high throughput tissue microarrays to detect heterogeneous protein expression. Hum Pathol. 31:406–414. 2000. View Article : Google Scholar

26 

Amato RJ, Logothetis CJ, Hallinan R, Ro JY, Sella A and Dexeus FH: Chemotherapy for small cell carcinoma of prostatic origin. J Urol. 147:935–937. 1992.PubMed/NCBI

27 

Komiya A, Yasuda K, Nozaki T, Fujiuchi Y, Hayashi S and Fuse H: Small cell carcinoma of the prostate after high-dose-rate brachytherapy for low-risk prostatic adenocarcinoma. Oncol Lett. 5:53–56. 2013.PubMed/NCBI

28 

Rizzardi AE, Johnson AT, Vogel RI, Pambuccian SE, Henriksen J, Skubitz AP, Metzger GJ and Schmechel SC: Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring. Diagn Pathol. 7:422012. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Komiya A, Yasuda K, Watanabe A, Fujiuchi Y, Tsuzuki T and Fuse H: The prognostic significance of loss of the androgen receptor and neuroendocrine differentiation in prostate biopsy specimens among castration-resistant prostate cancer patients. Mol Clin Oncol 1: 257-262, 2013.
APA
Komiya, A., Yasuda, K., Watanabe, A., Fujiuchi, Y., Tsuzuki, T., & Fuse, H. (2013). The prognostic significance of loss of the androgen receptor and neuroendocrine differentiation in prostate biopsy specimens among castration-resistant prostate cancer patients. Molecular and Clinical Oncology, 1, 257-262. https://doi.org/10.3892/mco.2013.69
MLA
Komiya, A., Yasuda, K., Watanabe, A., Fujiuchi, Y., Tsuzuki, T., Fuse, H."The prognostic significance of loss of the androgen receptor and neuroendocrine differentiation in prostate biopsy specimens among castration-resistant prostate cancer patients". Molecular and Clinical Oncology 1.2 (2013): 257-262.
Chicago
Komiya, A., Yasuda, K., Watanabe, A., Fujiuchi, Y., Tsuzuki, T., Fuse, H."The prognostic significance of loss of the androgen receptor and neuroendocrine differentiation in prostate biopsy specimens among castration-resistant prostate cancer patients". Molecular and Clinical Oncology 1, no. 2 (2013): 257-262. https://doi.org/10.3892/mco.2013.69
Copy and paste a formatted citation
x
Spandidos Publications style
Komiya A, Yasuda K, Watanabe A, Fujiuchi Y, Tsuzuki T and Fuse H: The prognostic significance of loss of the androgen receptor and neuroendocrine differentiation in prostate biopsy specimens among castration-resistant prostate cancer patients. Mol Clin Oncol 1: 257-262, 2013.
APA
Komiya, A., Yasuda, K., Watanabe, A., Fujiuchi, Y., Tsuzuki, T., & Fuse, H. (2013). The prognostic significance of loss of the androgen receptor and neuroendocrine differentiation in prostate biopsy specimens among castration-resistant prostate cancer patients. Molecular and Clinical Oncology, 1, 257-262. https://doi.org/10.3892/mco.2013.69
MLA
Komiya, A., Yasuda, K., Watanabe, A., Fujiuchi, Y., Tsuzuki, T., Fuse, H."The prognostic significance of loss of the androgen receptor and neuroendocrine differentiation in prostate biopsy specimens among castration-resistant prostate cancer patients". Molecular and Clinical Oncology 1.2 (2013): 257-262.
Chicago
Komiya, A., Yasuda, K., Watanabe, A., Fujiuchi, Y., Tsuzuki, T., Fuse, H."The prognostic significance of loss of the androgen receptor and neuroendocrine differentiation in prostate biopsy specimens among castration-resistant prostate cancer patients". Molecular and Clinical Oncology 1, no. 2 (2013): 257-262. https://doi.org/10.3892/mco.2013.69
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team