Skip to main content
SpringerLink
Log in

Bcl-2 immunoreactivity in prostate tumorigenesis in relation to prostatic intraepithelial neoplasia, grade, hormonal status, metastatic growth and survival

  • Original Paper
  • Published:
Urological Research Aims and scope Submit manuscript

Abstract

The Bcl-2 protein prolongs cell survival by overriding apoptosis. To explore the role of Bcl-2 in prostate tumorigenesis, immunoreactivity for Bcl-2 was examined in untreated and androgen-deprived tumours and lymph node metastasis. Following the transurethral resection, 150 untreated patients were maintained under surveillance until death or for a minimum of 11 years, and castration was performed at symptomatic progression. The Bcl-2 index (BI) was defined as the percentage of immunoreactive cells in a tumour. The mean BI was 12 in the untreated tumours, and BI was significantly higher in high-grade tumours, mean BI 17, than in low-grade tumours, mean BI 6. There was no correlation between BI and stage or metastatic disease, nor did BI predict cancer-specific survival. In 16 androgen-deprived, but non-relapsed tumours, the mean BI was 54, at a mean time of 22 months after castration, indicating a permanent increase of Bcl-2 protein expression after androgen withdrawal. In six patients, tissues from the prostate tumour and obturator lymph node metastasis were available. Four primary tumours immunostained for Bcl-2, but only one metastasis stained. Foci of high-grade prostatic intraepithelial neoplasia (PIN) were present in 44 of the 150 untreated tumours. All PIN foci were intensely immunoreactive for Bcl-2, and mean BI was 79, suggesting that Bcl-2 protein expression is associated with early prostate tumorigenesis.

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. Berges RR, Vukanovic J, Epstein JI, CarMichel M, Cisek L, Johnson DE, Veltri RW, Walsh PC, Isaacs JT (1995) Implication of cell kinetic changes during the progression of human prostatic cancer. Clin Cancer Res 1:473

    Google Scholar 

  2. Brawer MK (1992) Prostatic intraepithelial neoplasia: a premalignant lesion. Hum Pathol 23:242

    Google Scholar 

  3. Bronner MP, Culin C, Reed JC, Furth EE (1995) The bcl-2 proto-oncogene and the gastrointestinal epithelial tumor progression model. Am J Pathol 146:20

    Google Scholar 

  4. Cambell MJ, Machin D (1993) Medical Statistics. Wiley, Chichester

    Google Scholar 

  5. Castle VP, Heidelberger KP, Bromberg J, Ou XG, Dole M, Nunez G (1993) Expression of the apoptosis-suppressing protein bcl-2 in neuroblastoma is associated with unfavorable histology and N-myc amplification. Am J Pathol 143:1543

    Google Scholar 

  6. Chiarodo A (ed) (1991) Prostate cancer working group: National Cancer Institute round table on prostate cancer: future research directions. Cancer Res 51:2498

  7. Colombel M, Symmans F, Gil S, Otoole KM, Chopin D, Benson M, Olsson CA, Korsmeyer S, Buttyan R (1993) Detection of the apoptosis-suppressing oncoprotein bcl-2 in hormone-refractory human prostate cancers. Am J Pathol 143:390

    Google Scholar 

  8. Craig RW (1995) The bcl-2 gene family. Semin Cancer Biol 6:35

    Google Scholar 

  9. Ferguson J, Zincke H, Ellison E, Bergstrahl E, Bostwick DG (1994) Decrease of prostatic intraepithelial neoplasia following androgen deprivation therapy in patients with stage T3 carcinoma treated by radical prostatectomy. Urology 44:91

    Google Scholar 

  10. Gompel A, Sabourin JC, Martin A, Yaneva H, Audouin J, Decroix Y, Poitout P (1994) Bcl-2 expression in normal endometrium during the menstrual cycle. Am J Pathol 144:1195

    Google Scholar 

  11. Grönberg H, Bergh A, Damber J-E, Jonnson H, Lenner P, Ångström T (1994) Prostate cancer in northern Sweden. Incidence, survival and mortality in relation to tumour grade. Acta Oncol 33:359

    Google Scholar 

  12. Hockenberry D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ (1990) Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348:334

    Google Scholar 

  13. Hockenberry DM, Zutter M, Hickey W, Nahm M, Korsmeyer SJ (1991) Bcl-2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc Natl Acad Sci USA 88:6961

    Google Scholar 

  14. Joensuu H, Pylkkanen L, Toikkanen S (1994) Bcl-2 protein expression and long-term survival in breast cancer. Am J Pathol 145:1191

    Google Scholar 

  15. Krajewski S, Blomqvist C, Franssila K, Krajewska M, Wasenius V-M, Niskanen E, Nordling S, Reed JC (1995) Reduced expression of proapoptotic gene bax is associated with poor response rates to combination chemotherapy and shorter survival in women with metastatic breast adenocarcinoma. Cancer Res 55:4471

    Google Scholar 

  16. Lauwers GY, Scott GV, Hendricks J (1994) Immunohistochemical evidence of aberrant bcl-2 protein expression in gastric epithelial dysplasia. Cancer 73:2900

    Google Scholar 

  17. Leek RD, Kaklamanis L, Pezzella F, Gatter KC, Harris AL (1994) bcl-2 in normal human breast and carcinoma, association with oestrogen receptor-positive, epidermal growth factor receptor-negative tumours and in situ cancer. Br J Cancer 69:135

    Google Scholar 

  18. Lu-Yao GL, Greenberg ER (1994) Changes in prostate cancer incidence and treatment in USA. Lancet 343:251

    Google Scholar 

  19. McDonnell TJ, Nunez G, Platt FM, Hockenberry D, London L, McKearn JP, Korsmeyer SJ (1990) Deregulated Bcl-2-immunoglobulin transgene expands a resting but responsive immunoglobulin M and D expressing B-cell population. Mol Cell Biol 10:1901

    Google Scholar 

  20. McDonnell TJ, Troncoso P, Brisbay SM, Logothetis C, Chung LWK, Hsieh JT, Tu SM, Campbell ML (1992) Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. Cancer Res 52:6940

    Google Scholar 

  21. McNeal JE, Bostwick DG (1986) Intraductal dysplasia: a premalignant lesion of the prostate. Hum Pathol 17:64

    Google Scholar 

  22. Mostofi FK, Sesterhenn IA, Sobin LH (1980) International histological classification of prostate tumours. In: Mostofi FK (ed) International histological classification of prostate tumours. WHO, Geneva

    Google Scholar 

  23. Norusis MJ (1993) SPSS for Windows, SPSS Inc, Chicago

    Google Scholar 

  24. Pilotti S, Collini P, Rilke F, Cattoretti G, Delbo R, Pierotti MA (1994) bcl-2 protein expression in carcinomas originating from the follicular epithelium of the thyroid gland. J Pathol 172:337

    Google Scholar 

  25. Raffo AJ, Perlman H, Chen M-W, Day ML, Streitman JS, Buttyan R (1995) Overexpression of bcl-2 protects prostate cancer cells from apoptosis in vitro and confers resistance to androgen depletion in vivo. Cancer Res 55:4438

    Google Scholar 

  26. Reed JC (1995) Bcl-2: prevention of apoptosis as a mechanism of drug resistance. Hematol/Oncol Clin North Am 9:451

    Google Scholar 

  27. Rinker-Schaeffer CW, Isaacs WB, Isaacs JT (1993) Molecular and cellular markers for metastatic prostate cancer. Cancer Metastasis Rev 12:3

    Google Scholar 

  28. Sabourin JC, Martin A, Baruch J, Truc JB, Gompel A, Poitout P (1994) bcl-2 expression in normal breast tissue during the menstrual cycle. Int J Cancer 59:1

    Google Scholar 

  29. Shi SR, Key ME, Kalra KL (1991) Antigen retrieval in formalinfixed paraffin embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem 39:741

    Google Scholar 

  30. Silvestrini R, Veneroni S, Daidone MG, Benini E, Boracchi P, Mezzetti M, Di Fronzo G, Rilke F, Veronesi U (1994) The Bcl-2 protein: a prognostic indicator strongly related to p53 protein in lymph node-negative breast cancer patients. J Natl Cancer Inst 86:499

    Google Scholar 

  31. Sinicrope FA, Ruan SB, Cleary KR, Stephens LC, Lee JJ,Levin B (1995) bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. Cancer Res 55:237

    Google Scholar 

  32. Tron VA, Krajewski S, Klein-Parker H, Li G, Ho VC, Reed JC (1995) Immunohistochemical analysis of bcl-2 protein regulation in cutaneous melanoma. Am J Pathol 146:643

    Google Scholar 

  33. UICC (Union Internationale Contre le Cancer) (1978) TNM classification of malignant tumours, 2 edn. Springer, Berlin Heidelberg New York

    Google Scholar 

  34. Vaux D, Cory S, Adams J (1988) Bcl-2 gene promotes haematopoetic cell survival and co-operates with c-myc to immortalize B cells. Nature 335:440

    Google Scholar 

  35. Viale G, Roncalilli M, Grimelius L, Graziani D, Wilander E, Johansson H, Bergholm U, Coggi G (1995) Prognostic value of Bcl-2 immunoreactivity in medullary thyroid carcinoma. Hum Pathol 26:945

    Google Scholar 

  36. Westin P, Stattin P, Damber J-E, Bergh A (1995) Castration therapy rapidly induces apoptosis in a minority and decreases cell proliferation in a majority of human prostatic tumors. Am J Pathol 146:1368

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology and Andrology, Umeå University, S-901 85, Umeå, Sweden

    P. Stattin & J. -E. Damber

  2. Department of Urology, Central Hospital, Västerås, Sweden

    L. Karlberg

  3. Department of Pathology, Uppsala University, Sweden

    H. Nordgren

  4. Department of Pathology, Umeå University, Sweden

    A. Bergh

Authors
  1. P. Stattin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. -E. Damber
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Karlberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Nordgren
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Bergh
    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

Stattin, P., Damber, J.E., Karlberg, L. et al. Bcl-2 immunoreactivity in prostate tumorigenesis in relation to prostatic intraepithelial neoplasia, grade, hormonal status, metastatic growth and survival. Urol. Res. 24, 257–264 (1996). https://doi.org/10.1007/BF00304774

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00304774

Key words

Search

Navigation