Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

Does true Gleason pattern 3 merit its cancer descriptor?

Nature Reviews Urology volume 13, pages 541–548 (2016)Cite this article

Subjects

Abstract

Nearly five decades following its conception, the Gleason grading system remains a cornerstone in the prognostication and management of patients with prostate cancer. In the past few years, a debate has been growing whether Gleason score 3 + 3 = 6 prostate cancer is a clinically significant disease. Clinical, molecular and genetic research is addressing the question whether well characterized Gleason score 3 + 3 = 6 disease has the ability to affect the morbidity and quality of life of an individual in whom it is diagnosed. The consequences of treatment of Gleason score 3 + 3 = 6 disease are considerable; few men get through their treatments without sustaining some harm. Further modification of the classification of prostate cancer and dropping the label cancer for Gleason score 3 + 3 = 6 disease might be warranted.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The pathological, clinical and molecular differences between Gleason pattern 3 and 4 disease.
Figure 2: The five-point grade group system of Gleason scoring.

Similar content being viewed by others

References

  1. Jemal, A. et al. Cancer statistics, 2006. CA Cancer J. Clin. 56, 106–130 (2006).

    PubMed  Google Scholar 

  2. Humphrey, P. A. Gleason grading and prognostic factors in carcinoma of the prostate. Mod. Pathol. 17, 292–306 (2004).

    PubMed  Google Scholar 

  3. Gleason, D. F. Classification of prostatic carcinomas. Cancer Chemother. Rep. 50, 125–128 (1966).

    CAS  PubMed  Google Scholar 

  4. Xu, W. & Zhou, M. A concise update on prostate pathology. Cesk. Patol. 50, 120–128 (2014).

    PubMed  Google Scholar 

  5. Esserman, L., Shieh, Y. & Thompson, I. Rethinking screening for breast cancer and prostate cancer. JAMA 302, 1685–1692 (2009).

    CAS  PubMed  Google Scholar 

  6. Nickel, J. C. & Speakman, M. Should we really consider Gleason 6 prostate cancer? BJU Int. 109, 645–646 (2012).

    PubMed  Google Scholar 

  7. Klotz, L. Cancer overdiagnosis and overtreatment. Curr. Opin. Urol. 22, 203–209 (2012).

    PubMed  Google Scholar 

  8. Lepor, H. & Donin, N. M. Gleason 6 prostate cancer: serious malignancy or toothless lion? Oncol. (Williston Park) 28, 16–22 (2014).

    Google Scholar 

  9. Gleason, D. F. & Mellinger, G. T. Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J. Urol. 111, 58–64 (1974).

    CAS  PubMed  Google Scholar 

  10. Delahunt, B., Miller, R. J., Srigley, J. R., Evans, A. J. & Samaratunga, H. Gleason grading: past, present and future. Histopathology 60, 75–86 (2012).

    PubMed  Google Scholar 

  11. Montironi, R. et al. Original Gleason system versus 2005 ISUP modified Gleason system: the importance of indicating which system is used in the patient's pathology and clinical reports. Eur. Urol. 58, 369–373 (2010).

    PubMed  Google Scholar 

  12. Allsbrook, W. C. Jr et al. Interobserver reproducibility of Gleason grading of prostatic carcinoma: urologic pathologists. Hum. Pathol. 32, 74–80 (2001).

    PubMed  Google Scholar 

  13. Oyama, T. et al. A comparison of interobserver reproducibility of Gleason grading of prostatic carcinoma in Japan and the United States. Arch. Pathol. Lab. Med. 129, 1004–1010 (2005); erratum 129, 1368 (2005).

    PubMed  Google Scholar 

  14. Shah, R. B. Current perspectives on the Gleason grading of prostate cancer. Arch. Pathol. Lab. Med. 133, 1810–1816 (2009).

    PubMed  Google Scholar 

  15. Epstein, J. I. An update of the Gleason grading system. J. Urol. 183, 433–440 (2010).

    PubMed  Google Scholar 

  16. Epstein, J. I. Gleason score 2–4 adenocarcinoma of the prostate on needle biopsy: a diagnosis that should not be made. Am. J. Surg. Pathol. 24, 477–478 (2000).

    CAS  PubMed  Google Scholar 

  17. Ghani, K. R., Grigor, K., Tulloch, D. N., Bollina, P. R. & McNeill, S. A. Trends in reporting Gleason score 1991 to 2001: changes in the pathologist's practice. Eur. Urol. 47, 196–201 (2005).

    PubMed  Google Scholar 

  18. Helpap, B. & Egevad, L. The significance of modified Gleason grading of prostatic carcinoma in biopsy and radical prostatectomy specimens. Virchows Arch. 449, 622–627 (2006).

    PubMed  Google Scholar 

  19. Epstein, J. I., Allsbrook, W. C. Jr, Amin, M. B. & Egevad, L. L. The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am. J. Surg. Pathol. 29, 1228–1242 (2005).

    PubMed  Google Scholar 

  20. Albertsen, P. C. et al. Prostate cancer and the Will Rogers phenomenon. J. Natl Cancer Inst. 97, 1248–1253 (2005).

    PubMed  Google Scholar 

  21. Berg, K. D. et al. The impact of the 2005 International Society of Urological Pathology consensus guidelines on Gleason grading - a matched-pair analysis. BJU Int. 117, 883–889 (2016).

    PubMed  Google Scholar 

  22. Silletti, J. P., Gordon, G. J., Bueno, R., Jaklitsch, M. & Loughlin, K. R. Prostate biopsy: past, present, and future. Urology 69, 413–416 (2007).

    PubMed  Google Scholar 

  23. Eichler, K. et al. Diagnostic value of systematic biopsy methods in the investigation of prostate cancer: a systematic review. J. Urol. 175, 1605–1612 (2006).

    PubMed  Google Scholar 

  24. Mai, Z. et al. Transperineal template-guided prostate biopsy: 10 years of experience. BJU Int. 117, 426–429 (2014).

    Google Scholar 

  25. Moore, C. M. et al. Image-guided prostate biopsy using magnetic resonance imaging-derived targets: a systematic review. Eur. Urol. 63, 125–140 (2013).

    PubMed  Google Scholar 

  26. Shariat, S. F. & Roehrborn, C. G. Using biopsy to detect prostate cancer. Rev. Urol. 10, 262–280 (2008).

    PubMed  PubMed Central  Google Scholar 

  27. Bostwick, D. G. Evaluating prostate needle biopsy: therapeutic and prognostic importance. CA Cancer J. Clin. 47, 297–319 (1997).

    CAS  PubMed  Google Scholar 

  28. Shaw, G. L. et al. Identification of pathologically insignificant prostate cancer is not accurate in unscreened men. Br. J. Cancer 110, 2405–2411 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Kasivisvanathan, V. et al. Transperineal magnetic resonance image targeted prostate biopsy versus transperineal template prostate biopsy in the detection of clinically significant prostate cancer. J. Urol. 189, 860–866 (2013).

    PubMed  Google Scholar 

  30. Siddiqui, M. M. et al. Magnetic resonance imaging/ultrasound-fusion biopsy significantly upgrades prostate cancer versus systematic 12-core transrectal ultrasound biopsy. Eur. Urol. 64, 713–719 (2013).

    PubMed  PubMed Central  Google Scholar 

  31. Fine, S. W. & Epstein, J. I. A contemporary study correlating prostate needle biopsy and radical prostatectomy Gleason score. J. Urol. 179, 1335–1338; discussion 1338–1339 (2008).

    PubMed  Google Scholar 

  32. Capitanio, U. et al. Biopsy core number represents one of foremost predictors of clinically significant Gleason sum upgrading in patients with low-risk prostate cancer. Urology 73, 1087–1091 (2009).

    PubMed  Google Scholar 

  33. Epstein, J. I., Feng, Z., Trock, B. J. & Pierorazio, P. M. Upgrading and downgrading of prostate cancer from biopsy to radical prostatectomy: incidence and predictive factors using the modified Gleason grading system and factoring in tertiary grades. Eur. Urol. 61, 1019–1024 (2012).

    PubMed  PubMed Central  Google Scholar 

  34. Epstein, J. I., Sanderson, H., Carter, H. B. & Scharfstein, D. O. Utility of saturation biopsy to predict insignificant cancer at radical prostatectomy. Urology 66, 356–360 (2005).

    PubMed  Google Scholar 

  35. Sved, P. D., Gomez, P., Manoharan, M., Kim, S. S. & Soloway, M. S. Limitations of biopsy Gleason grade: implications for counseling patients with biopsy Gleason score 6 prostate cancer. J. Urol. 172, 98–102 (2004).

    PubMed  Google Scholar 

  36. Emiliozzi, P. et al. Increased accuracy of biopsy Gleason score obtained by extended needle biopsy. J. Urol. 172, 2224–2226 (2004).

    CAS  PubMed  Google Scholar 

  37. Nayyar, R. et al. Upgrading of Gleason score on radical prostatectomy specimen compared to the preoperative needle core biopsy: an Indian experience. Indian J. Urol. 26, 56–59 (2010).

    PubMed  PubMed Central  Google Scholar 

  38. Marks, L., Young, S. & Natarajan, S. MRI-ultrasound fusion for guidance of targeted prostate biopsy. Curr. Opin. Urol. 23, 43–50 (2013).

    PubMed  PubMed Central  Google Scholar 

  39. Ahmed, H. U. The PROMIS of MRI. BJU Int. 118, 7 (2016).

    PubMed  Google Scholar 

  40. Griffiths, D. F. et al. A study of Gleason score interpretation in different groups of UK pathologists; techniques for improving reproducibility. Histopathology 48, 655–662 (2006).

    CAS  PubMed  Google Scholar 

  41. Penney, K. L. et al. Gleason grade progression is uncommon. Cancer Res. 73, 5163–5168 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Sonn, G. A. et al. Initial experience with electronic tracking of specific tumour sites in men undergoing active surveillance of prostate cancer. Urol. Oncol. 32, 952–957 (2014).

    PubMed  PubMed Central  Google Scholar 

  43. Robertson, N. L. et al. MAPPED study design: a 6 month randomised controlled study to evaluate the effect of dutasteride on prostate cancer volume using magnetic resonance imaging. Contemp. Clin. Trials 34, 80–89 (2013).

    CAS  PubMed  Google Scholar 

  44. Mufarrij, P., Sankin, A., Godoy, G. & Lepor, H. Pathologic outcomes of candidates for active surveillance undergoing radical prostatectomy. Urology 76, 689–692 (2010).

    PubMed  Google Scholar 

  45. Albertsen, P. C., Hanley, J. A. & Fine, J. 20-year outcomes following conservative management of clinically localized prostate cancer. JAMA 293, 2095–2101 (2005).

    CAS  PubMed  Google Scholar 

  46. Popiolek, M. et al. Natural history of early, localized prostate cancer: a final report from three decades of follow-up. Eur. Urol. 63, 428–435 (2013).

    PubMed  Google Scholar 

  47. Schiffmann, J. et al. Tumour volume in insignificant prostate cancer: increasing threshold gains increasing risk. Prostate 75, 45–49 (2015).

    CAS  PubMed  Google Scholar 

  48. Eggener, S. E. et al. Predicting 15-year prostate cancer specific mortality after radical prostatectomy. J. Urol. 185, 869–875 (2011).

    PubMed  PubMed Central  Google Scholar 

  49. Ross, H. M. et al. Do adenocarcinomas of the prostate with Gleason score (GS) ≤6 have the potential to metastasize to lymph nodes? Am. J. Surg. Pathol. 36, 1346–1352 (2012).

    PubMed  PubMed Central  Google Scholar 

  50. Wilt, T. J. et al. Radical prostatectomy versus observation for localized prostate cancer. N. Engl. J. Med. 367, 203–213 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Brower, V. Researchers tackle metastasis, cancer's last frontier. J. Natl Cancer Inst. 99, 109–111 (2007).

    PubMed  Google Scholar 

  52. Datta, K., Muders, M., Zhang, H. & Tindall, D. J. Mechanism of lymph node metastasis in prostate cancer. Future Oncol. 6, 823–836 (2010).

    PubMed  Google Scholar 

  53. Cai, T. et al. Clinical importance of lymph node density in predicting outcome of prostate cancer patients. J. Surg. Res. 167, 267–272 (2011).

    PubMed  Google Scholar 

  54. Liu, J. J. et al. Nationwide prevalence of lymph node metastases in Gleason score 3 + 3 = 6 prostate cancer. Pathology 46, 306–310 (2014).

    PubMed  Google Scholar 

  55. Bubendorf, L. et al. Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum. Pathol. 31, 578–583 (2000).

    CAS  PubMed  Google Scholar 

  56. Lee, N. et al. Which patients with newly diagnosed prostate cancer need a radionuclide bone scan? An analysis based on 631 patients. Int. J. Radiat. Oncol. Biol. Phys. 48, 1443–1446 (2000).

    CAS  PubMed  Google Scholar 

  57. Ting, F. et al. Tumour volume in insignificant prostate cancer: Increasing the threshold is a safe approach to reduce over-treatment. Prostate 75, 1768–1773 (2015).

    PubMed  Google Scholar 

  58. Nakabayashi, M. et al. Clinical predictors of survival in men with castration-resistant prostate cancer: evidence that Gleason score 6 cancer can evolve to lethal disease. Cancer 119, 2990–2998 (2013).

    PubMed  Google Scholar 

  59. Haffner, M. C. et al. Tracking the clonal origin of lethal prostate cancer. J. Clin. Invest. 123, 4918–4922 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. El-Shater Bosaily, A., Arya, M. & Ahmed, H. Clinical predictors of survival in men with castration-resistant prostate cancer: evidence that Gleason score 6 cancer can evolve to lethal disease. Cancer 119, 4052–4053 (2013).

    PubMed  Google Scholar 

  61. Hayes, J. H., Nakabayashi, M. & Kantoff, P. W. Reply to clinical predictors of survival in men with castration-resistant prostate cancer: evidence that Gleason score 6 cancer can evolve to lethal disease. Cancer 119, 4053 (2013).

    PubMed  Google Scholar 

  62. Passoni, N. M. & Polascik, T. J. Words of wisdom. Re: tracking the clonal origin of lethal prostate cancer. Eur. Urol. 66, 390–391 (2014).

    PubMed  Google Scholar 

  63. Brannon, A. R. & Sawyers, C. L. “N of 1” case reports in the era of whole-genome sequencing. J. Clin. Invest. 123, 4568–4570 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57–70 (2000).

    CAS  PubMed  Google Scholar 

  65. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).

    CAS  PubMed  Google Scholar 

  66. Ahmed, H. U., Arya, M., Freeman, A. & Emberton, M. Do low-grade and low-volume prostate cancers bear the hallmarks of malignancy? Lancet Oncol. 13, e509–e517 (2012).

    PubMed  Google Scholar 

  67. Miah, S. & Catto, J. W. MicroRNA in prostate cancer: an opportunity to individualize patient care. J. Urol. 187, 1155–1156 (2012).

    PubMed  Google Scholar 

  68. Miah, S., Pang, K. & Catto, J. W. MicroRNA and urothelial cell carcinoma. BJU Int. 113, 811–812 (2014).

    PubMed  Google Scholar 

  69. Catto, J. W. et al. Distinct microRNA alterations characterize high- and low-grade bladder cancer. Cancer Res. 69, 8472–8481 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. VanderWeele, D. J. et al. Low-grade prostate cancer diverges early from high grade and metastatic disease. Cancer Sci. 105, 1079–1085 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Lavery, H. J. & Droller, M. J. Do Gleason patterns 3 and 4 prostate cancer represent separate disease states? J. Urol. 188, 1667–1675 (2012).

    PubMed  Google Scholar 

  72. Berndt, S. I. et al. Two susceptibility loci identified for prostate cancer aggressiveness. Nat. Commun. 6, 6889 (2015).

    CAS  PubMed  Google Scholar 

  73. Shen, M. M. & Abate-Shen, C. Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev. 24, 1967–2000 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Penney, K. L. et al. mRNA expression signature of Gleason grade predicts lethal prostate cancer. J. Clin. Oncol. 29, 2391–2396 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. True, L. et al. A molecular correlate to the Gleason grading system for prostate adenocarcinoma. Proc. Natl Acad. Sci. USA 103, 10991–10996 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Tomlins, S. A. et al. Integrative molecular concept modelling of prostate cancer progression. Nat. Genet. 39, 41–51 (2007).

    CAS  PubMed  Google Scholar 

  77. Cooper, C. S. et al. Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue. Nat. Genet. 47, 367–372 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Barbieri, C. E., Demichelis, F. & Rubin, M. A. The lethal clone in prostate cancer: redefining the index. Eur. Urol. 66, 395–397 (2014).

    PubMed  Google Scholar 

  79. Allegra, C. J. et al. NIH state-of-the-science conference statement: diagnosis and management of ductal carcinoma in situ (DCIS). NIH Consens. State Sci. Statements 26, 1–27 (2009).

    PubMed  Google Scholar 

  80. Allegra, C. J. et al. National Institutes of Health State-of-the-Science Conference statement: Diagnosis and Management of Ductal Carcinoma In Situ September 22–24, 2009. J. Natl Cancer Inst. 102, 161–169 (2010).

    PubMed  Google Scholar 

  81. Ito, Y. et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid 13, 381–387 (2003).

    PubMed  Google Scholar 

  82. Piersanti, M., Ezzat, S. & Asa, S. L. Controversies in papillary microcarcinoma of the thyroid. Endocr. Pathol. 14, 183–191 (2003).

    PubMed  Google Scholar 

  83. Perros, P. et al. Guidelines for the management of thyroid cancer. Clin. Endocrinol. 81 (Suppl. 1), 1–122 (2014).

    CAS  Google Scholar 

  84. Schwartz, L. M. & Woloshin, S. Changing disease definitions: implications for disease prevalence. Analysis of the Third National Health and Nutrition Examination Survey, 1988–1994. Eff. Clin. Pract. 2, 76–85 (1999).

    CAS  PubMed  Google Scholar 

  85. Martin, S. A., Boucher, M., Wright, J. M. & Saini, V. Mild hypertension in people at low risk. BMJ 349, g5432 (2014).

    PubMed  Google Scholar 

  86. Schroeder, A. R. & Redberg, R. F. Cholesterol screening and management in children and young adults should start early — NO! Clin. Cardiol. 35, 665–668 (2012).

    PubMed  PubMed Central  Google Scholar 

  87. Lipska, K. J. et al. Potential overtreatment of diabetes mellitus in older adults with tight glycaemic control. JAMA Intern. Med. 175, 356–362 (2015).

    PubMed  PubMed Central  Google Scholar 

  88. Epstein, J. I., Amin, M. B., Reuter, V. R. & Mostofi, F. K. The World Health Organization/International Society of Urologicasl Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. Am. J. Surg. Pathol. 22, 1435–1448 (1998).

    CAS  PubMed  Google Scholar 

  89. Fujii, Y., Kawakami, S., Koga, F., Nemoto, T. & Kihara, K. Long-term outcome of bladder papillary urothelial neoplasms of low malignant potential. BJU Int. 92, 559–562 (2003).

    CAS  PubMed  Google Scholar 

  90. MacLennan, G. T., Kirkali, Z. & Cheng, L. Histologic grading of noninvasive papillary urothelial neoplasms. Eur. Urol. 51, 889–897; discussion 897–888 (2007).

    PubMed  Google Scholar 

  91. Bastian, P. J. et al. Insignificant prostate cancer and active surveillance: from definition to clinical implications. Eur. Urol. 55, 1321–1330 (2009).

    PubMed  Google Scholar 

  92. Moynihan, R., Doust, J. & Henry, D. Preventing overdiagnosis: how to stop harming the healthy. BMJ 344, e3502 (2012).

    PubMed  Google Scholar 

  93. Klotz, L. Prostate cancer overdiagnosis and overtreatment. Curr. Opin. Endocrinol. Diabetes Obes. 20, 204–209 (2013).

    CAS  PubMed  Google Scholar 

  94. Daskivich, T. J. et al. Variation in treatment associated with life expectancy in a population-based cohort of men with early-stage prostate cancer. Cancer 120, 3642–3650 (2014).

    PubMed  Google Scholar 

  95. Hoffman, K. E. et al. Physician variation in management of low-risk prostate cancer: a population-based cohort study. JAMA Intern. Med. 174, 1450–1459 (2014).

    PubMed  PubMed Central  Google Scholar 

  96. Shao, Y. H. et al. Risk profiles and treatment patterns among men diagnosed as having prostate cancer and a prostate-specific antigen level below 4.0 ng/ml. Arch. Intern. Med. 170, 1256–1261 (2010).

    PubMed  PubMed Central  Google Scholar 

  97. Aizer, A. A. et al. Cost implications and complications of overtreatment of low-risk prostate cancer in the United States. J. Natl Compr. Canc. Netw. 13, 61–68 (2015).

    PubMed  Google Scholar 

  98. van der Kwast, T. H. & Roobol, M. J. Prostate cancer: is prostatectomy for Gleason score 6 a treatment failure? Nat. Rev. Urol. 12, 10–11 (2015).

    PubMed  Google Scholar 

  99. Barry, J. M. Words of wisdom. Re: radical prostatectomy versus observation for localized prostate cancer. Eur. Urol. 62, 1196 (2012).

    PubMed  Google Scholar 

  100. Carter, H. B. et al. Gleason score 6 adenocarcinoma: should it be labelled as cancer? J. Clin. Oncol. 30, 4294–4296 (2012).

    PubMed  PubMed Central  Google Scholar 

  101. Mahal, B. A. et al. Who bears the greatest burden of aggressive treatment of indolent prostate cancer? Am. J. Med. 128, 609–616 (2015).

    PubMed  Google Scholar 

  102. Osman, N. I. & Collins, G. N. Urological litigation in the UK National Health Service (NHS): an analysis of 14 years of successful claims. BJU Int. 108, 162–165 (2011).

    PubMed  Google Scholar 

  103. Dunn, I. B. & Kirk, D. Legal pitfalls in the diagnosis of prostate cancer. BJU Int. 86, 304–307 (2000).

    CAS  PubMed  Google Scholar 

  104. Brown, C. T. et al. The fear of prostate cancer in men with lower urinary tract symptoms: should symptomatic men be screened? BJU Int. 91, 30–32 (2003).

    CAS  PubMed  Google Scholar 

  105. Berger, Z. D., Yeh, J. C., Carter, H. B. & Pollack, C. E. Characteristics and experiences of patients with localized prostate cancer who left an active surveillance program. Patient 7, 427–436 (2014).

    PubMed  PubMed Central  Google Scholar 

  106. Carrion, I. V., Nedjat-Haiem, F. R. & Marquez, D. X. Examining cultural factors that influence treatment decisions: a pilot study of Latino men with cancer. J. Cancer Educ. 28, 729–737 (2013).

    PubMed  Google Scholar 

  107. Epstein, J. I. et al. A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur. Urol. 69, 428–435 (2015).

    PubMed  PubMed Central  Google Scholar 

  108. Ross, A. E. et al. Gene expression pathways of high grade localized prostate cancer. Prostate 71, 1568–1577 (2011).

    CAS  PubMed  Google Scholar 

  109. Skacel, M. et al. Aneusomy of chromosomes 7, 8, and 17 and amplification of HER-2/neu and epidermal growth factor receptor in Gleason score 7 prostate carcinoma: a differential fluorescent in situ hybridization study of Gleason pattern 3 and 4 using tissue microarray. Hum. Pathol. 32, 1392–1397 (2001).

    CAS  PubMed  Google Scholar 

  110. Padar, A. et al. Inactivation of cyclin D2 gene in prostate cancers by aberrant promoter methylation. Clin. Cancer Res. 9, 4730–4734 (2003).

    CAS  PubMed  Google Scholar 

  111. Fleischmann, A. et al. Prognostic relevance of Bcl-2 overexpression in surgically treated prostate cancer is not caused by increased copy number or translocation of the gene. Prostate 72, 991–997 (2012).

    CAS  PubMed  Google Scholar 

  112. Hendriksen, P. J. et al. Evolution of the androgen receptor pathway during progression of prostate cancer. Cancer Res. 66, 5012–5020 (2006).

    CAS  PubMed  Google Scholar 

  113. West, A. F., O'Donnell, M., Charlton, R. G., Neal, D. E. & Leung, H. Y. Correlation of vascular endothelial growth factor expression with fibroblast growth factor-8 expression and clinico-pathologic parameters in human prostate cancer. Br. J. Cancer 85, 576–583 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. de Muga, S. et al. CXCR4 mRNA overexpression in high grade prostate tumours: lack of association with TMPRSS2-ERG rearrangement. Cancer Biomark. 12, 21–30 (2012).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Mark Emberton holds Senior Investigator status with the UK National Institute for Health Research (NIHR). He receives research support from the NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.

Author information

Authors and Affiliations

  1. Hashim U. Ahmed and Mark Emberton are at the Division of Surgery and Interventional Science, Saiful Miah, University College London Medical School Building, 21 University Street, London WC1E 6AU, UK.,

    Saiful Miah, Hashim U. Ahmed & Mark Emberton

  2. Alex Freeman is at the Department of Pathology, University College London Hospital, 3rd Floor East, 250 Euston Road, London NW1 2PG, UK.,

    Alex Freeman

Authors
  1. Saiful Miah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hashim U. Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alex Freeman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mark Emberton
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to researching data for the article, discussing its content, writing the article and reviewing and editing the manuscript before submission.

Corresponding author

Correspondence to Mark Emberton.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Miah, S., Ahmed, H., Freeman, A. et al. Does true Gleason pattern 3 merit its cancer descriptor?. Nat Rev Urol 13, 541–548 (2016). https://doi.org/10.1038/nrurol.2016.141

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrurol.2016.141

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing