Human Pathology
Volume 41, Issue 6 , Pages 781-793 , June 2010

Multifocal prostate cancer: biologic, prognostic, and therapeutic implications

  • Matei Andreoiu, MD

      Affiliations

    • Department of Urology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
  • ,
  • Liang Cheng, MD

      Affiliations

    • Department of Urology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    • Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    • Corresponding Author InformationCorresponding author. Departments of Pathology and Urology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Received 13 November 2009 ,Revised 21 February 2010 ,Accepted 25 February 2010.

References 

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–249
  2. Bastacky SI, Wojno KJ, Walsh PC, Carmichael MJ, Epstein JI. Pathological features of hereditary prostate cancer. J Urol. 1995;153:987–992
  3. Kastendieck H. Correlations between atypical primary hyperplasia and carcinoma of the prostate. A histological study of 180 total prostatectomies. Pathol Res Pract. 1980;169:366–387
  4. Cheng L, Poulos CK, Pan C, et al. Preoperative prediction of small volume cancer (<0.5 ml) in radical prostatectomy specimens. J Urol. 2005;174:898–902
  5. Byar DP, Mostofi FK. Carcinoma of the prostate: prognostic evaluation of certain pathologic features in 208 radical prostatectomies. Cancer. 1972;30:5–13
  6. Cheng L, Jones TD, Pan CX, Barbarin A, Eble JN, Koch MO. Anatomic distribution and pathologic characterization of small-volume prostate cancer (<0.5 ml) in whole-mount prostatectomy specimens. Mod Pathol. 2005;18:1022–1026
  7. Greene DR, Wheeler TM, Egawa S, Weaver RP, Scardino PT. Relationship between clinical stage and histological zone of origin in early prostate cancer: morphometric analysis. Br J Urol. 1991;68:499–509
  8. Qian J, Bostwick DG. The extent and zonal location of prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia: relationship with carcinoma in radical prostatectomy specimens. Pathol Res Pract. 1995;191:860–867
  9. Eichelberger LE, Cheng L. Does pT2b prostate carcinoma exist? Critical appraisal of the 2002 TNM classification of prostate carcinoma. Cancer. 2004;100:2573–2576
  10. Arora R, Koch MO, Eble JN, Ulbright TM, Li L, Cheng L. Heterogeneity of Gleason grade in multifocal adenocarcinoma of the prostate. Cancer. 2004;100:2362–2366
  11. Cheng L, Song S, Pretlow TG, et al. Evidence of independent origin of multiple tumors from patients with prostate cancer. J Natl Can Inst. 1998;90:233–237
  12. Villers A, McNeal JE, Freiha FS, Stamey TA. Multiple cancers in the prostate. Cancer. 1992;70:2313–2318
  13. Cheng L, Pisansky TM, Ramnani DM, et al. Extranodal extension in lymph node-positive prostate cancer. Mod Pathol. 2000;13:113–118
  14. Miller GJ, Cygan JM. Morphology of prostate cancer: the effect of multifocality on histological grade, tumor volume, and capsule penetration. J Urol. 1994;152:1709–1713
  15. Aihara M, Wheeler TM, Ohori M, Scardino PT. Heterogeneity of prostate cancer in radical prostatectomy specimens. Urology. 1994;43:60–67
  16. Bostwick DG, Shan A, Qian J, et al. Independent origin of multiple foci of prostatic intraepithelial neoplasia: comparison with matched foci of prostate carcinoma. 1998;83:1995-2002.
  17. Ruijter E, Van de Kaa CA, Schalken JA, Debruyne FR, Ruiter DJ. Histological grade heterogeneity in multifocal prostate cancer: biological and clinical implications. J Pathol. 1996;180:295–299
  18. von Eschenbach AC. The biologic dilemma of early carcinoma of the prostate. Cancer. 1996;78:326–329
  19. Liu W, Laitinen S, Khan S, et al. Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer. Nat Med. 2009;15:559–565
  20. Zaridze DG, Boyle P. Cancer of the prostate: epidemiology and aetiology. Br J Urol. 1987;59:493–502
  21. Cooney KA, McCarthy JD, Lange E, et al. Prostate cancer susceptibility locus on chromosome 1q: a confirmatory study. J Natl Cancer Inst. 1997;89:955–959
  22. Monroe KR, Yu MC, Kolonel LN, et al. Evidence of an X-linked or recessive genetic component to prostate cancer risk. Nat Med. 1995;1:827–829
  23. Smith JR, Freije D, Carpten JD, et al. Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search. Science. 1996;274:1371–1374
  24. Whittemore AS, Wu AH, Kolonel LN, et al. Family history and prostate cancer risk in black, white, and Asian men in the United States and Canada. Am J Epidemiol. 1995;141:732–740
  25. Isaacs SD, Kiemeney LA, Baffoe-Bonnie A, Beaty TH, Walsh PC. Risk of cancer in relatives of prostate cancer probands. J Natl Cancer Inst. 1995;87:991–996
  26. Stellman SD, Wang QS. Cancer mortality in Chinese immigrants to New York City. Comparison with Chinese in Tianjin and with United States-born whites. Cancer. 1994;73:1270–1275
  27. Fischer N, Hellwinkel O, Schulz C, et al. Prevalence of human gammaretrovirus XMRV in sporadic prostate cancer. J Clin Virol. 2008;43:277–283
  28. Schlaberg R, Choe DJ, Brown KR, Thaker HM, Singh IR. XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors. Proc Natl Acad Sci USA. 2009;106:16351–16356
  29. De Marzo AM, Platz EA, Sutcliffe S, et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer. 2007;4:256–269
  30. Epstein JI. Precursor lesions to prostatic adenocarcinoma. Virchows Arch. 2009;454:1–16
  31. Gleason DF. Histologic grading of prostate cancer: a perspective. Hum Pathol. 1992;23:273–279
  32. Gleason DF. Classification of prostatic carcinomas. Cancer Chemother Rep. 1966;50:125–128
  33. Gleason DF, Mellinger GT. Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. Veterans administration cooperative urologic research group. J Urol. 1974;111:58–64
  34. McNeal JE, Bostwick DG, Kindrachuk RA, Redwine EA, Freiha FS, Stamey TA. Patterns of progression in prostate cancer. Lancet. 1986;1:60–63
  35. Stamey TA. Clinical and morphometric observations on prostate cancer. Med Sect Proc. 1988;29–42
  36. Brawn PN. The dedifferentiation of prostate carcinoma. Cancer. 1983;52:246–251
  37. Cheng L, Bergstralh EJ, Slezak J, Cheville JC, Zincke H, Bostwick DG. Dedifferentiation in metastatic progression of prostate cancer. Cancer. 1999;86:657–663
  38. McNeal JE. Regional morphology and pathology of the prostate. Am J Clin Pathol. 1968;49:347–357
  39. McNeal JE. The zonal anatomy of the prostate. Prostate. 1981;2:35–49
  40. McNeal JE. Cancer volume and site of origin of adenocarcinoma in the prostate: relationship to local and distant spread. Hum Pathol. 1992;23:258–266
  41. McNeal JE, Redwine EA, Freiha FS, Stamey TA. Zonal distribution of prostatic adenocarcinoma: correlation with histologic pattern and direction of spread. Am J Surg Pathol. 1988;12:897–906
  42. Garcia JJ, Al-Ahmadie HA, Gopalan A, et al. Do prostatic transition zone tumors have a distinct morphology?. Am J Surg Pathol. 2008;32:1709–1714
  43. Greene DR, Wheeler TM, Egawa S, Dunn JK, Scardino PT. A comparison of the morphological features of cancer arising in the transition zone and in the peripheral zone of the prostate. J Urol. 1991;146:1069–1076
  44. Augustin H, Erbersdobler A, Graefen M, et al. Differences in biopsy features between prostate cancers located in the transition and peripheral zone. BJU Int. 2003;91:477–481
  45. Stamey TA, Sozen TS, Yemoto CM, McNeal JE. Classification of localized untreated prostate cancer based on 791 men treated only with radical prostatectomy: common ground for therapeutic trials and TNM subgroups. J Urol. 1998;159:2009–2012
  46. Noguchi M, Stamey TA, McNeal JE, Yemoto CE. An analysis of 148 consecutive transition zone cancers: clinical and histological characteristics. J Urol. 2000;163:1751–1755
  47. Augustin H, Erbersdobler A, Graefen M, et al. Biochemical recurrence following radical prostatectomy: a comparison between prostate cancers located in different anatomical zones. Prostate. 2003;55:48–54
  48. Noguchi M, Stamey TA, McNeal JE, Nolley R. Prognostic factors for multifocal prostate cancer in radical prostatectomy specimens: lack of significance of secondary cancers. J Urol. 2003;170:459–463
  49. Steuber T, Karakiewicz PI, Augustin H, et al. Transition zone cancers undermine the predictive accuracy of Partin table stage predictions. J Urol. 2005;173:737–741
  50. Shannon BA, McNeal JE, Cohen RJ. Transition zone carcinoma of the prostate gland: a common indolent tumour type that occasionally manifests aggressive behaviour. Pathology. 2003;35:467–471
  51. Al-Ahmadie HA, Tickoo SK, Olgac S, et al. Anterior-predominant prostatic tumors: zone of origin and pathologic outcomes at radical prostatectomy. Am J Surg Pathol. 2008;32:229–235
  52. Chun FK, Briganti A, Jeldres C, et al. Zonal origin of localized prostate cancer does not affect the rate of biochemical recurrence after radical prostatectomy. Eur Urol. 2007;51:949–955[discussion 955]
  53. Sakai I, Harada K, Kurahashi T, Yamanaka K, Hara I, Miyake H. Analysis of differences in clinicopathological features between prostate cancers located in the transition and peripheral zones. Int J Urol. 2006;13:368–372
  54. Sakai I, Harada K, Hara I, Eto H, Miyake H. A comparison of the biological features between prostate cancers arising in the transition and peripheral zones. BJU Int. 2005;96:528–532
  55. Guo CC, Zuo G, Cao D, Troncoso P, Czemiak BA. Prostate cancer of transition zone origin lacks TMPRSS2-ERG gene fusion. Mod Pathol. 2009;22:866–871
  56. Bostwick DG, Meiers I. Neoplasms of the prostate. In:  Bostwick DG,  Cheng L editor. Urologic Surgical Pathology. 2nd ed.. Philadelphia: Elsevier/Mosby; 2008;p. 443–580
  57. Bostwick DG, Qian J. High-grade prostatic intraepithelial neoplasia. Mod Pathol. 2004;17:360–379
  58. Cheng L, Paterson RF, Beck SD, Parks J. Prostatic intraepithelial neoplasia: an update. Clin Prostate Cancer. 2004;3:26–30
  59. Montironi R, Mazzucchelli R, Lopez-Beltran A, Cheng L, Scarpelli M. Mechanisms of disease: high-grade prostatic intraepithelial neoplasia and other proposed preneoplastic lesions in the prostate. Nat Clin Pract Urol. 2007;4:321–332
  60. Qian J, Jenkins RB, Bostwick DG. Detection of chromosomal anomalies and c-myc gene amplification in the cribriform pattern of prostatic intraepithelial neoplasia and carcinoma by fluorescence in situ hybridization. Mod Pathol. 1997;10:1113–1119
  61. Greene DR, Taylor SR, Wheeler TM, Scardino PT. DNA ploidy by image analysis of individual foci of prostate cancer: a preliminary report. Cancer Res. 1991;51:4084–4089
  62. Emmert-Buck MR, Vocke CD, Pozzatti RO, et al. Allelic loss on chromosome 8p12-21 in microdissected prostatic intraepithelial neoplasia. Cancer Res. 1995;55:2959–2962
  63. Sakr WA, Macoska JA, Benson P, et al. Allelic loss in locally metastatic, multisampled prostate cancer. Cancer Res. 1994;54:3273–3277
  64. Qian J, Bostwick DG, Takahashi S, et al. Chromosomal anomalies in prostatic intraepithelial neoplasia and carcinoma detected by fluorescence in situ hybridization. Cancer Res. 1995;55:5408–5414
  65. Emi M, Fujiwara Y, Nakajima T, et al. Frequent loss of heterozygosity for loci on chromosome 8p in hepatocellular carcinoma, colorectal cancer, and lung cancer. Cancer Res. 1992;52:5368–5372
  66. Cunningham J, Lust JA, Schaid DJ, et al. Expression of p53 and 17p allelic loss in colorectal carcinoma. Cancer Res. 1992;52:1974–1980
  67. Yaremko ML, Wasylyshyn ML, Paulus KL, Michelassi F, Westbrook CA. Deletion mapping reveals two regions of chromosome 8 allele loss in colorectal carcinomas. Genes Chromosomes Cancer. 1994;10:1–6
  68. Fujiwara Y, Monden M, Mori T, Nakamura Y, Emi M. Frequent multiplication of the long arm of chromosome 8 in hepatocellular carcinoma. Cancer Res. 1993;53:857–860
  69. Knowles MA, Shaw ME, Proctor AJ. Deletion mapping of chromosome 8 in cancers of the urinary bladder using restriction fragment length polymorphisms and microsatellite polymorphisms. Oncogene. 1993;8:1357–1364
  70. Kobayashi M, Ishida H, Shindo T, et al. Molecular analysis of multifocal prostate cancer by comparative genomic hybridization. Prostate. 2008;68:1715–1724
  71. Tomlins SA, Mehra R, Rhodes DR, et al. Integrative molecular concept modeling of prostate cancer progression. Nat Genet. 2007;39:41–51
  72. Ahmed HU. The index lesion and the origin of prostate cancer. N EnglJ Med. 2009;361:1704–1706
  73. Gurel B, Iwata T, Koh CM, et al. Nuclear MYC protein overexpression is an early alteration in human prostate carcinogenesis. Mod Pathol. 2008;21:1156–1167
  74. Kumar-Sinha C, Tomlins SA, Chinnaiyan AM. Recurrent gene fusions in prostate cancer. Nat Rev Cancer. 2008;8:497–511
  75. True L, Coleman I, Hawley S, et al. A molecular correlate to the Gleason grading system for prostate adenocarcinoma. Proc Natl Acad Sci USA. 2006;103:10991–10996
  76. Jenkins RB, Qian J, Lieber MM, Bostwick DG. Detection of c-myc oncogene amplification and chromosomal anomalies in metastatic prostatic carcinoma by fluorescence in situ hybridization. Cancer Res. 1997;57:524–531
  77. Schmidt H, DeAngelis G, Eltze E, Gockel I, Semjonow A, Brandt B. Asynchronous growth of prostate cancer is reflected by circulating tumor cells delivered from distinct, even small foci, harboring loss of heterozygosity of the PTEN gene. Cancer Res. 2006;66:8959–8965
  78. Tomlins SA, Mehra R, Rhodes DR, et al. TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer. Cancer Res. 2006;66:3396–3400
  79. Tomlins SA, Rhodes DR, Perner S, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310:644–648
  80. Mehra R, Han B, Tomlins SA, et al. Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases. Cancer Res. 2007;67:7991–7995
  81. Soller MJ, Isaksson M, Elfving P, Soller W, Lundgren R, Panagopoulos I. Confirmation of the high frequency of the TMPRSS2/ERG fusion gene in prostate cancer. Genes Chromosomes Cancer. 2006;45:717–719
  82. Perner S, Demichelis F, Beroukhim R, et al. TMPRSS2:ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. Cancer Res. 2006;66:8337–8341
  83. Perner S, Mosquera JM, Demichelis F, et al. TMPRSS2-ERG fusion prostate cancer: an early molecular event associated with invasion. Am J Surg Pathol. 2007;31:882–888
  84. Demichelis F, Fall K, Perner S, et al. TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene. 2007;26:4596–4599
  85. Barry M, Perner S, Demichelis F, Rubin MA. TMPRSS2-ERG fusion heterogeneity in multifocal prostate cancer: clinical and biologic implications. Urology. 2007;70:630–633
  86. Wang J, Cai Y, Ren C, Ittmann M. Expression of variant TMPRSS2/ERG fusion messenger RNAs is associated with aggressive prostate cancer. Cancer Res. 2006;66:8347–8351
  87. Gopalan A, Leversha MA, Satagopan JM, et al. TMPRSS2-ERG gene fusion is not associated with outcome in patients treated by prostatectomy. Cancer Res. 2009;69:1400–1406
  88. Saramaki OR, Harjula AE, Martikainen PM, Vessella RL, Tammela TL, Visakorpi T. TMPRSS2:ERG fusion identifies a subgroup of prostate cancers with a favorable prognosis. Clin Cancer Res. 2008;14:3395–3400
  89. Henrique R, Jeronimo C, Teixeira MR, et al. Epigenetic heterogeneity of high-grade prostatic intraepithelial neoplasia: clues for clonal progression in prostate carcinogenesis. Mol Cancer Res. 2006;4:1–8
  90. Henrique R, Jeronimo C, Hoque MO, et al. MT1G hypermethylation is associated with higher tumor stage in prostate cancer. Cancer Epidemiol Biomarkers Prev. 2005;14:1274–1278
  91. Jeronimo C, Henrique R, Hoque MO, et al. A quantitative promoter methylation profile of prostate cancer. Clin Cancer Res. 2004;10:8472–8478
  92. Cheville JC, Karnes RJ, Therneau TM, et al. Gene panel model predictive of outcome in men at high-risk of systemic progression and death from prostate cancer after radical retropubic prostatectomy. J Clin Oncol. 2008;26:3930–3936
  93. Beahrs OH, Henson DE, Hutter RVP, Kennedy BJ. AJCC Manual for staging of cancer. 4th ed.. Philadelphia: Lippincott; 1992;
  94. Catalona WJ. Management of cancer of the prostate. N Engl J Med. 1994;331:996–1004
  95. Catalona WJ, Smith DS. Detection of early prostate cancer: serendipitous or systematic?. JAMA. 1998;279:1439–1441
  96. Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999;281:1591–1597
  97. Zincke H, Oesterling JE, Blute ML, Bergstralh EJ, Myers RP, Barrett DM. Long-term (15 years) results after radical prostatectomy for clinically localized (stage T2c or lower) prostate cancer. J Urol. 1994;152:1850–1857
  98. Fleming ID, Phillips JL, Menck HR, Murphy GP, Winchester DP. The National Cancer Data Base report on recent hospital cancer program progress toward complete American Joint Committee on Cancer/TNM staging. Cancer. 1997;80:2305–2310
  99. Cagiannos I, Graefen M, Karakiewicz PI, et al. Analysis of clinical stage T2 prostate cancer: Do current subclassifications represent an improvement?. J Clin Oncol. 2002;20:2025–2030
  100. Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. American Joint Committee on Cancer Staging Manual. 7th ed.. New York: Springer; 2010;
  101. Greene FL, Page DL, Flemming ID, et al. American Joint Committee on Cancer Staging Manual. 6th ed.. New York: Springer-Verlag; 2002;
  102. Han M, Walsh PC, Partin AW, Rodriguez R. Ability of the 1992 and 1997 American Joint Committee on Cancer Staging Systems for prostate cancer to predict progression-free survival after radical prostatectomy for stage T2 disease. J Urol. 2000;164:89–92
  103. Iyer RV, Hanlon AL, Pinover WH, Hanks GE. Outcome evaluation of the 1997 American Joint Committee on Cancer staging system for prostate carcinoma treated by radiation therapy. Cancer. 1999;85:1816–1821
  104. Bostwick DG, Myers RP, Oesterling JE. Staging of prostate cancer. Semin Surg Oncol. 1994;10:60–72
  105. Hoedemaeker RF, Vis AN, Van der Kwast TH. Staging prostate cancer. Microsc Res Tech. 2000;51:423–429
  106. Pan C, Potter SR, Partin AW, Epstein JI. The prognostic significance of tertiary Gleason patterns of higher grade in radical prostatectomy specimens: a proposal to modify the Gleason grading system. Am J Surg Pathol. 2000;24:563–569
  107. Chan TY, Partin AW, Walsh PC, Epstein JI. Prognostic significance of Gleason score 3+4 versus Gleason score 4+3 tumor at radical prostatectomy. Urology. 2000;56:823–827
  108. Hattab EM, Koch MO, Eble JN, Lin H, Cheng L. Tertiary Gleason pattern 5 is a powerful predictor of biochemical relapse in patients with Gleason score 7 prostatic adenocarcinoma. J Urol. 2006;175:1695–1699
  109. Sim HG, Telesca D, Culp SH, et al. Tertiary Gleason pattern 5 in Gleason 7 prostate cancer predicts pathological stage and biochemical recurrence. J Urol. 2008;179:1775–1779
  110. Patel AA, Chen MH, Renshaw AA, D'Amico AV. PSA failure following definitive treatment of prostate cancer having biopsy Gleason score 7 with tertiary grade 5. JAMA. 2007;298:1533–1538
  111. Harnden P, Shelley MD, Coles B, Staffurth J, Mason MD. Should the Gleason grading system for prostate cancer be modified to account for high-grade tertiary components? A systematic review and meta-analysis. Lancet Oncol. 2007;8:411–419
  112. Trock BJ, Guo CC, Gonzalgo ML, Magheli A, Loeb S, Epstein JI. Tertiary Gleason patterns and biochemical recurrence after prostatectomy: proposal for a modified Gleason scoring system. J Urol. 2009;182:1364–1370
  113. Stamey TA, McNeal JE, Yemoto CM, Sigal BM, Johnstone IM. Biological determinants of cancer progression in men with prostate cancer. JAMA. 1999;281:1395–1400
  114. Cheng L, Koch MO, Juliar BE, et al. The combined percentage of Gleason patterns 4 and 5 is the best predictor of cancer progression after radical prostatectomy. J Clin Oncol. 2005;23:2911–2917
  115. Cheng L, Davidson DD, Lin H, Koch MO. Percentage of Gleason pattern 4 and 5 predicts survival after radical prostatectomy. Cancer. 2007;110:1967–1972
  116. Gburek BM, Kollmorgen TA, Qian J, D'Souza-Gburek SM, Lieber MM, Jenkins RB. Chromosomal anomalies in stage D1 prostate adenocarcinoma primary tumors and lymph node metastases detected by fluorescence in situ hybridization. J Urol. 1997;157:223–227
  117. Djavan B, Susani M, Bursa B, Basharkhah A, Simak R, Marberger M. Predictability and significance of multifocal prostate cancer in the radical prostatectomy specimen. Tech Urol. 1999;5:139–142
  118. Polascik TJ, Mouraviev V. Focal therapy for prostate cancer is a reasonable treatment option in properly selected patients. Urology. 2009;74:726–730
  119. Koch MO, Gardner T, Cheng L, Fedewa RJ, Seip R, Sanghvi NT. Phase I/II trial of high intensity focused ultrasound for the treatment of previously untreated localized prostate cancer. J Urol. 2007;178:2366–2371
  120. Barqawi A, Crawford ED. Focal therapy in prostate cancer: future trends. BJU Int. 2005;95:273–274
  121. Hövels AM, Heesakkers RA, Adang EM, et al. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clin Radiol. 2008;63:387–395
  122. Cupp MR, Bostwick DG, Myers RP, Oesterling JE. The volume of prostate cancer in the biopsy specimen cannot reliably predict the quantity of cancer in the radical prostatectomy specimen on an individual basis. J Urol. 1995;153:1543–1548
  123. Leibovich BC, Blute ML, Bostwick DG, et al. Proximity of prostate cancer to the urethra: implications for minimally invasive ablative therapies. Urology. 2000;56:726–729
  124. Chen ME, Johnston DA, Tang K, Babaian RJ, Troncoso P. Detailed mapping of prostate carcinoma foci: biopsy strategy implications. Cancer. 2000;89:1800–1809
  125. Erbersdobler A, Huhle S, Palisaar J, et al. Pathological and clinical characteristics of large prostate cancers predominantly located in the transition zone. Prostate Cancer Prostatic Dis. 2002;5:279–284

PII: S0046-8177(10)00108-5

doi: 10.1016/j.humpath.2010.02.011

Human Pathology
Volume 41, Issue 6 , Pages 781-793 , June 2010