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p16INK4a, PTEN, E-cadherin, Bcl-2 and Ki-67 Expression in Prostate Cancer: Its Relationship with the Metastatic Potential and Known Prognostic Factors

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Background : At present, adequate prognostic markers for prostate cancer progression are still lacking, in spite of intensive investigation. Accordingly, our study examined the relationship between expression of candidate biomarkers and metastasis in prostate cancer patients. Correlation of molecular markers with prostate-specific antigen (PSA) level, Gleason sum score and tumor stage were also evaluated. Methods : A total of 105 prostate tumor specimens and specimens from 19 cases of nodular hyperplasia were obtained through Yeungnam University Hospital from 2007 to 2008. Immunohistochemical analyses for p16INK4a, phosphatase and tensin homolog (PTEN), E-cadherin, Ki-67 and Bcl-2 were performed. Results : Overexpression of Bcl-2 was significantly related to bone (p = 0.006) and nodal metastases (p = 0.017). Other biomarkers were not related to metastatic potential. There were statistically significant relationships between increased PSA level and loss of expression of PTEN (p = 0.019) and E-cadherin (p = 0.001). High Ki-67 index was significantly correlated with nodal metastasis (p = 0.029) as well as with loss of p16INK4a expression (p = 0.002) and high Gleason score (p = 0.011). Conclusions : High Gleason score, Bcl-2 overexpression and increased Ki-67 labeling have significant predictive value in assessing the potential for prostate cancer metastasis. In addition, a high Ki-67 index is related to high Gleason score and loss of p16INK4a expression.

Abstract

Background : At present, adequate prognostic markers for prostate cancer progression are still lacking, in spite of intensive investigation. Accordingly, our study examined the relationship between expression of candidate biomarkers and metastasis in prostate cancer patients. Correlation of molecular markers with prostate-specific antigen (PSA) level, Gleason sum score and tumor stage were also evaluated. Methods : A total of 105 prostate tumor specimens and specimens from 19 cases of nodular hyperplasia were obtained through Yeungnam University Hospital from 2007 to 2008. Immunohistochemical analyses for p16INK4a, phosphatase and tensin homolog (PTEN), E-cadherin, Ki-67 and Bcl-2 were performed. Results : Overexpression of Bcl-2 was significantly related to bone (p = 0.006) and nodal metastases (p = 0.017). Other biomarkers were not related to metastatic potential. There were statistically significant relationships between increased PSA level and loss of expression of PTEN (p = 0.019) and E-cadherin (p = 0.001). High Ki-67 index was significantly correlated with nodal metastasis (p = 0.029) as well as with loss of p16INK4a expression (p = 0.002) and high Gleason score (p = 0.011). Conclusions : High Gleason score, Bcl-2 overexpression and increased Ki-67 labeling have significant predictive value in assessing the potential for prostate cancer metastasis. In addition, a high Ki-67 index is related to high Gleason score and loss of p16INK4a expression.

참고문헌 (30)

  1. Jemal A, "Cancer statistics,2008", CA Cancer J Clin, 58, pp.71~96 (2008)
  2. [URL]
  3. Stamey TA, "Preoperative serum prostate specific antigen levels between 2 and 22 ng.", ml.correlate poorly with post-radical prostatectomy cancer morphology:prostate specific antigen cure rates appear constant between 2 and 9 ng., J Urol, pp.2002, 167[DOI]
  4. Quinn DI, "Molecular markers of prostate cancer outcome", Eur J Cancer, 41, pp.858~887 (2005)
  5. McDonnell TJ, "Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer", Cancer Res, 52, pp.6940~6944 (1992)
  6. Mol AJ, "New experimental markers for early detection of high-risk prostate cancer:role of cell-cell adhesion and cell migration", J Cancer Res Clin Oncol, 133, pp.687~695 (2007)
  7. Epstein JI, "The 2005 International Society of Urological Pathology(ISUP)Consensus Conference on Gleason Grading of Prostatic Carcinoma", Am J Surg Pathol, 29, pp.1228~1242 (2005)
  8. Kattan MW, "The addition of interleukin-6 soluble receptor and transforming growth factor beta1 improves a preoperative nomogram for predicting biochemical progression in patients with clinically localized prostate cancer", J Clin Oncol, 21, pp.3573~3579 (2003)
  9. Sentman CL, "bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes", Cell, 67, pp.879~888 (1991)
  10. Merseburger AS, "Limitations of tissue microarrays in the evaluation of focal alterations of bcl-2 and p53 in whole mount derived prostate tissues", Oncol Rep, 10, pp.223~228 (2003)
  11. Revelos K, "Immunohistochemical expression of Bcl2 is an independent predictor of time-to-biochemical failure in patients with clinically localized prostate cancer following radical prostatectomy", Anticancer Res, 25, pp.3123~3133 (2005)
  12. Nariculam J, "Utility of tissue microarrays for profiling prognostic biomarkers in clinically localized prostate cancer:the expression of BCL-2,E-cadherin,Ki-67 and p53 as predictors of biochemical failure after radical prostatectomy with nest-ed control for clinical and pathological risk factors", Asian J Androl, 11, pp.109~118 (2009)
  13. Bray K, "Bcl-2 modulation to activate apoptosis in prostate cancer", Mol Cancer Res, 7, pp.1487~1496 (2009)
  14. Smith AJ, "Expression of the Bcl-2 protein BAD promotes prostate cancer growth", PLoS One, 4, pp.e6224~ (2009)
  15. Royuela M, "Immunoexpressions of p21,Rb,mcl-1 and bad gene products in normal,hyperplastic and carcinomatous human prostates", Eur Cytokine Netw, 12, pp.654~663 (2001)
  16. McDonnell TJ, "Biomarker expression patterns that correlate with high grade features in treatment naive,organ-confined prostate cancer", BMC Med Genomics, 1, pp.1~ (2008)
  17. Iemelynova AA, "Correlation between histological type and immunohistochemical profile of prostate cancer and gleason scale gradation", Exp Oncol, 31, pp.246~249 (2009)
  18. Rubin MA, "Ecadherin expression in prostate cancer:a broad survey using highdensity tissue microarray technology", Hum Pathol, 32, pp.690~697 (2001)
  19. Rhodes DR, "Multiplex biomarker approach for determining risk of prostate-specific antigen-defined recurrence of prostate cancer", J Natl Cancer Inst, 95, pp.661~668 (2003)
  20. Jaggi M, "Aberrant expression of E-cadherin and beta-catenin in human prostate cancer", Urol Oncol, 23, pp.402~406 (2005)
  21. Whitaker HC, "Alterations in beta-catenin expression and localization in prostate cancer", Prostate, 68, pp.1196~1205 (2008)
  22. Shah GV, "Cadherin switching and activation of beta-catenin signaling underlie proinvasive actions of calcitonin-calcitonin receptor axis in prostate cancer", J Biol Chem, 284, pp.1018~1030 (2009)
  23. Chakravarti A, "Loss of p16 expression is of prognostic significance in locally advanced prostate cancer:an analysis from the Radiation Therapy Oncology Group protocol 86-10", J Clin Oncol, 21, pp.3328~3334 (2003)
  24. Chakravarti A, "Prognostic value of p16 in locally advanced prostate cancer:a study based on Radiation Therapy Oncology Group Protocol 9202", J Clin Oncol, 25, pp.3082~3089 (2007)
  25. Zhang Z, "Expression of p14ARF,p15INK4b,p16INK4a,and DCR2 increases during prostate cancer progression", Mod Pathol, 19, pp.1339~1343 (2006)
  26. Jarrard DF, "Alterations in the p16", pRb cell cycle checkpoint occur commonly in primary and metastatic human prostate cancer, 2002, pp.185, 191~199
  27. Schmitz M, "Complete loss of PTEN expression as a possible early prognostic marker for prostate cancer metastasis", Int J Cancer, 120, pp.1284~1292 (2007)
  28. Wu Z, "The role of PTEN in prostate cancer cell tropism to the bone micro-environment", Carcinogenesis, 28, pp.1393~1400 (2007)
  29. Bedolla R, "Determining risk of biochemical recurrence in prostate cancer by immunohistochemical detection of PTEN expression and Akt activation", Clin Cancer Res, 13, pp.3860~3867 (2007)
  30. Bubendorf L, "Ki67 labelling index:an independent predictor of progression in prostate cancer treated by radical prostatectomy", J Pathol, 178, pp.437~441 (1996)

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