Skip to main content

Advertisement

SpringerLink
Log in

Apparent differences in prostate zones: susceptibility to prostate cancer, benign prostatic hyperplasia and prostatitis

  • Urology - Review
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Men are inevitably plagued by prostate disease throughout their lives. However, the understanding of the pathogenesis of prostate diseases is still limited. In the 1960s, McNeal proposed the theory of prostate zones: the prostate was divided into three main zones: transition zone, central zone, and peripheral zone. Over the past 50 years, significant differences between different prostate zones have been gradually revealed. We summarized the most significant differences in different zones of the prostate. For the first time, we proposed the “apparent difference in prostate zones” concept. This new concept has been proposed to understand the different zones of the prostate better. It also provided new ideas for exploring the susceptibility of lesions in different prostate zones. Despite the reported differences between zones, the treatment of prostate-related diseases remains partition agnostic. Therefore, we also discussed the clinical significance of the “apparent difference in the prostate zone” and emphasized the necessity of prostate zones.

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

Data availability

Data availability is not applicable to this article as no new data were created in this study.

References

  1. Villers A, Steg A, Boccon-Gibod L (1991) Anatomy of the prostate: review of the different models. Eur Urol 20:261–268. https://doi.org/10.1159/000471714

    Article  CAS  PubMed  Google Scholar 

  2. Foster HE, Barry MJ, Dahm P et al (2018) Surgical management of lower urinary tract symptoms attributed to benign prostatic hyperplasia: AUA guideline. J Urol 200:612–619. https://doi.org/10.1016/j.juro.2018.05.048

    Article  PubMed  Google Scholar 

  3. Lerner LB, McVary KT, Barry MJ et al (2021) Management of lower urinary tract symptoms attributed to benign prostatic hyperplasia: AUA guideline PART I-initial work-up and medical management. J Urol 206:806–817. https://doi.org/10.1097/JU.0000000000002183

    Article  PubMed  Google Scholar 

  4. Clemens JQ, Meenan RT, O’Keeffe Rosetti MC et al (2005) Incidence and clinical characteristics of national institutes of health type III prostatitis in the community. J Urol 174:2319–2322. https://doi.org/10.1097/01.ju.0000182152.28519.e7

    Article  PubMed  Google Scholar 

  5. Nickel JC, Nyberg LM, Hennenfent M (1999) Research guidelines for chronic prostatitis: consensus report from the first national institutes of health international prostatitis collaborative network. Urology 54:229–233. https://doi.org/10.1016/s0090-4295(99)00205-8

    Article  CAS  PubMed  Google Scholar 

  6. Schaeffer AJ (2002) Classification (traditional and National Institutes of Health) and demographics of prostatitis. Urology 60:5–6. https://doi.org/10.1016/s0090-4295(02)02292-6. (discussion 6–7.)

    Article  PubMed  Google Scholar 

  7. Marks LS, Roehrborn CG, Andriole GL (2006) Prevention of benign prostatic hyperplasia disease. J Urol 176:1299–1306. https://doi.org/10.1016/j.juro.2006.06.022

    Article  PubMed  Google Scholar 

  8. Siegel RL, Miller KD, Fuchs HE et al (2022) Cancer statistics, 2022. CA Cancer J Clin 72:7–33. https://doi.org/10.3322/caac.21708

    Article  PubMed  Google Scholar 

  9. Sung H, Ferlay J, Siegel RL et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249. https://doi.org/10.3322/caac.21660

    Article  PubMed  Google Scholar 

  10. Krieger JN, Lee SWH, Jeon J et al (2008) Epidemiology of prostatitis. Int J Antimicrob Agents 31(Suppl 1):S85-90. https://doi.org/10.1016/j.ijantimicag.2007.08.028

    Article  CAS  PubMed  Google Scholar 

  11. McNeal JE (1968) Regional morphology and pathology of the prostate. Am J Clin Pathol 49:347–357. https://doi.org/10.1093/ajcp/49.3.347

    Article  CAS  PubMed  Google Scholar 

  12. McNeal JE, Redwine EA, Freiha FS et al (1988) Zonal distribution of prostatic adenocarcinoma. correlation with histologic pattern and direction of spread. Am J Surg Pathol 12:897–906. https://doi.org/10.1097/00000478-198812000-00001

    Article  CAS  PubMed  Google Scholar 

  13. Lowsley OS (1912) The development of the human prostate gland with reference to the development of other structures at the neck of the urinary bladder. Am J Anat 13:299–349. https://doi.org/10.1002/aja.1000130303

    Article  Google Scholar 

  14. Lowsley OS, Venero AP (1954) Persistent anterior lobe of the prostate gland. J Urol 71:469–474. https://doi.org/10.1016/S0022-5347(17)67811-X

    Article  CAS  PubMed  Google Scholar 

  15. Franks LM (1953) Benign nodular hyperplasia of the prostate; a review. Ann R Coll Surg Engl 14:92–106

    CAS  PubMed  Google Scholar 

  16. McNeal JE (1981) Normal and pathologic anatomy of prostate. Urology 17:11–16

    CAS  PubMed  Google Scholar 

  17. McNeal JE (1981) The zonal anatomy of the prostate. Prostate 2:35–49. https://doi.org/10.1002/pros.2990020105

    Article  CAS  PubMed  Google Scholar 

  18. McNeal JE (1988) Normal histology of the prostate. Am J Surg Pathol 12:619–633. https://doi.org/10.1097/00000478-198808000-00003

    Article  CAS  PubMed  Google Scholar 

  19. Hricak H, Dooms GC, McNeal JE et al (1987) MR imaging of the prostate gland: normal anatomy. AJR Am J Roentgenol 148:51–58. https://doi.org/10.2214/ajr.148.1.51

    Article  CAS  PubMed  Google Scholar 

  20. McNeal JE, Leav I, Alroy J et al (1988) Differential lectin staining of central and peripheral zones of the prostate and alterations in dysplasia. Am J Clin Pathol 89:41–48. https://doi.org/10.1093/ajcp/89.1.41

    Article  CAS  PubMed  Google Scholar 

  21. Seifert AW, Harfe BD, Cohn MJ (2008) Cell lineage analysis demonstrates an endodermal origin of the distal urethra and perineum. Dev Biol 318:143–152. https://doi.org/10.1016/j.ydbio.2008.03.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. McNeal JE (1980) Anatomy of the prostate: an historical survey of divergent views. Prostate 1:3–13. https://doi.org/10.1002/pros.2990010103

    Article  CAS  PubMed  Google Scholar 

  23. Lee F, Torp-Pedersen ST, Carroll JT et al (1989) Use of transrectal ultrasound and prostate-specific antigen in diagnosis of prostatic intraepithelial neoplasia. Urology 34:4–8

    CAS  PubMed  Google Scholar 

  24. Toivanen R, Shen MM (2017) Prostate organogenesis: tissue induction, hormonal regulation and cell type specification. Development 144:1382–1398. https://doi.org/10.1242/dev.148270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Meikle AW, Stephenson RA, McWhorter WP et al (1995) Effects of age, sex steroids, and family relationships on volumes of prostate zones in men with and without prostate cancer. Prostate 26:253–259. https://doi.org/10.1002/pros.2990260505

    Article  CAS  PubMed  Google Scholar 

  26. Hammerer PG, McNeal JE, Stamey TA (1995) Correlation between serum prostate specific antigen levels and the volume of the individual glandular zones of the human prostate. J Urol 153:111–114. https://doi.org/10.1097/00005392-199501000-00038

    Article  CAS  PubMed  Google Scholar 

  27. Sharkey C, Long X, Wang Z et al (2022) Zonal growth pattern of the prostate Is affected by age and body mass index. J Urol 207:876–884. https://doi.org/10.1097/JU.0000000000002332

    Article  PubMed  Google Scholar 

  28. Meikle AW, Stephenson RA, Lewis CM et al (1997) Effects of age and sex hormones on transition and peripheral zone volumes of prostate and benign prostatic hyperplasia in twins. J Clin Endocrinol Metab 82:571–575. https://doi.org/10.1210/jcem.82.2.3720

    Article  CAS  PubMed  Google Scholar 

  29. Selman SH (2011) The McNeal prostate: a review. Urology 78:1224–1228. https://doi.org/10.1016/j.urology.2011.07.1395

    Article  PubMed  Google Scholar 

  30. Laczkó I, Hudson DL, Freeman A et al (2005) Comparison of the zones of the human prostate with the seminal vesicle: morphology, immunohistochemistry, and cell kinetics. Prostate 62:260–266. https://doi.org/10.1002/pros.20149

    Article  PubMed  Google Scholar 

  31. Augustin H, Erbersdobler A, Graefen M et al (2003) Differences in biopsy features between prostate cancers located in the transition and peripheral zone. BJU Int 91:477–481. https://doi.org/10.1046/j.1464-410x.2003.04140.x

    Article  CAS  PubMed  Google Scholar 

  32. Erbersdobler A, Fritz H, Schnöger S et al (2002) Tumour grade, proliferation, apoptosis, microvessel density, p53, and bcl-2 in prostate cancers: differences between tumours located in the transition zone and in the peripheral zone. Eur Urol 41:40–46. https://doi.org/10.1016/s0302-2838(01)00021-5

    Article  CAS  PubMed  Google Scholar 

  33. Shen P, Zhao J, Sun G et al (2017) The roles of prostate-specific antigen (PSA) density, prostate volume, and their zone-adjusted derivatives in predicting prostate cancer in patients with PSA less than 20.0 ng/mL. Andrology 5:548–555. https://doi.org/10.1111/andr.12322

    Article  CAS  PubMed  Google Scholar 

  34. Cohen RJ, Shannon BA, Phillips M et al (2008) Central zone carcinoma of the prostate gland: a distinct tumor type with poor prognostic features. J Urol 179:1762–1767. https://doi.org/10.1016/j.juro.2008.01.017. (discussion 1767)

    Article  PubMed  Google Scholar 

  35. Sakai I, Harada K-I, Hara I et al (2005) A comparison of the biological features between prostate cancers arising in the transition and peripheral zones. BJU Int 96:528–532. https://doi.org/10.1111/j.1464-410X.2005.05678.x

    Article  PubMed  Google Scholar 

  36. Iremashvili V, Pelaez L, Jordá M et al (2012) Prostate cancers of different zonal origin: clinicopathological characteristics and biochemical outcome after radical prostatectomy. Urology 80:1063–1069. https://doi.org/10.1016/j.urology.2012.08.012

    Article  PubMed  Google Scholar 

  37. Sakai I, Harada K-I, Kurahashi T et al (2006) Analysis of differences in clinicopathological features between prostate cancers located in the transition and peripheral zones. Int J Urol 13:368–372. https://doi.org/10.1111/j.1442-2042.2006.01307.x

    Article  PubMed  Google Scholar 

  38. Greene DR, Fitzpatrick JM, Scardino PT (1995) Anatomy of the prostate and distribution of early prostate cancer. Semin Surg Oncol 11:9–22. https://doi.org/10.1002/ssu.2980110104

    Article  CAS  PubMed  Google Scholar 

  39. Colombel M, Vacherot F, Diez SG et al (1998) Zonal variation of apoptosis and proliferation in the normal prostate and in benign prostatic hyperplasia. Br J Urol 82:380–385. https://doi.org/10.1046/j.1464-410x.1998.00752.x

    Article  CAS  PubMed  Google Scholar 

  40. Yu X, Liu R, Song L et al (2023) Differences in the pathogenetic characteristics of prostate cancer in the transitional and peripheral zones and the possible molecular biological mechanisms. Front Oncol 13:1165732. https://doi.org/10.3389/fonc.2023.1165732

    Article  PubMed  PubMed Central  Google Scholar 

  41. Yu X, Liu R, Gao W et al (2023) Single-cell omics traces the heterogeneity of prostate cancer cells and the tumor microenvironment. Cell Mol Biol Lett 28:38. https://doi.org/10.1186/s11658-023-00450-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhang T-H, Hu C-H, Chen J-X et al (2017) Differentiation diagnosis of hypo-intense T2 area in unilateral peripheral zone of prostate using magnetic resonance spectroscopy (MRS): prostate carcinoma versus prostatitis. Med Sci Monit 23:3837–3843. https://doi.org/10.12659/MSM.903123

    Article  PubMed  PubMed Central  Google Scholar 

  43. Doble A, Carter SS (1989) Ultrasonographic findings in prostatitis. Urol Clin North Am 16:763–772

    Article  CAS  PubMed  Google Scholar 

  44. Shukla-Dave A, Hricak H, Eberhardt SC et al (2004) Chronic prostatitis: MR imaging and 1H MR spectroscopic imaging findings–initial observations. Radiology 231:717–724. https://doi.org/10.1148/radiol.2313031391

    Article  PubMed  Google Scholar 

  45. Gerstenbluth RE, Seftel AD, MacLennan GT et al (2002) Distribution of chronic prostatitis in radical prostatectomy specimens with up-regulation of bcl-2 in areas of inflammation. J Urol 167:2267–2270

    Article  PubMed  Google Scholar 

  46. Packer JR, Maitland NJ (2016) The molecular and cellular origin of human prostate cancer. Biochim Biophys Acta 1863:1238–1260. https://doi.org/10.1016/j.bbamcr.2016.02.016

    Article  CAS  PubMed  Google Scholar 

  47. Henry GH, Malewska A, Joseph DB et al (2018) A cellular anatomy of the normal adult human prostate and prostatic urethra. Cell Rep 25:3530-3542.e5. https://doi.org/10.1016/j.celrep.2018.11.086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Shen MM, Abate-Shen C (2010) Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev 24:1967–2000. https://doi.org/10.1101/gad.1965810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Crowley L, Shen MM (2022) Heterogeneity and complexity of the prostate epithelium: new findings from single-cell RNA sequencing studies. Cancer Lett 525:108–114. https://doi.org/10.1016/j.canlet.2021.10.035

    Article  CAS  PubMed  Google Scholar 

  50. Karthaus WR, Hofree M, Choi D et al (2020) Regenerative potential of prostate luminal cells revealed by single-cell analysis. Science 368:497–505. https://doi.org/10.1126/science.aay0267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Levesque C, Nelson PS (2018) Cellular constituents of the prostate stroma key contributors to prostate cancer progression and therapy resistance. Cold Spring Harb Perspect Med. https://doi.org/10.1101/cshperspect.a030510

    Article  PubMed  PubMed Central  Google Scholar 

  52. Shiga K, Hara M, Nagasaki T et al (2015) Cancer-associated fibroblasts: their characteristics and their roles in tumor growth. Cancers (Basel) 7:2443–2458. https://doi.org/10.3390/cancers7040902

    Article  PubMed  Google Scholar 

  53. Chua CW, Shibata M, Lei M et al (2014) Single luminal epithelial progenitors can generate prostate organoids in culture. Nat Cell Biol 16(951–61):1–4. https://doi.org/10.1038/ncb3047

    Article  CAS  Google Scholar 

  54. Wang X, Xu H, Cheng C et al (2020) Identification of a Zeb1 expressing basal stem cell subpopulation in the prostate. Nat Commun 11:706. https://doi.org/10.1038/s41467-020-14296-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Zhang D, Zhao S, Li X et al (2018) Prostate luminal progenitor cells in development and cancer. Trends Cancer 4:769–783. https://doi.org/10.1016/j.trecan.2018.09.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Babinski MA, Chagas MA, Costa WS et al (2003) Prostatic epithelial and luminal area in the transition zone acini: morphometric analysis in normal and hyperplastic human prostate. BJU Int 92:592–596. https://doi.org/10.1046/j.1464-410x.2003.04433.x

    Article  CAS  PubMed  Google Scholar 

  57. Wernert N, Kern L, Heitz P et al (1990) Morphological and immunohistochemical investigations of the utriculus prostaticus from the fetal period up to adulthood. Prostate 17:19–30. https://doi.org/10.1002/pros.2990170104

    Article  CAS  PubMed  Google Scholar 

  58. Alves EF, Freitas Ribeiro BLM, de, Costa WS, et al (2018) Histological and quantitative analyzes of the stromal and acinar components of normal human prostate zones. Prostate 78:289–293. https://doi.org/10.1002/pros.23472

    Article  CAS  PubMed  Google Scholar 

  59. Powell MS, Li R, Dai H et al (2005) Neuroanatomy of the normal prostate. Prostate 65:52–57. https://doi.org/10.1002/pros.20245

    Article  PubMed  Google Scholar 

  60. Hynes PJ, Fraher JP (2004) The development of the male genitourinary system. I. the origin of the urorectal septum and the formation of the perineum. Br J Plast Surg 57:27–36. https://doi.org/10.1016/j.bjps.2003.08.019

    Article  CAS  PubMed  Google Scholar 

  61. Kellokumpu-Lehtinen P, Santti R, Pelliniemi LJ (1980) Correlation of early cytodifferentiation of the human fetal prostate and Leydig cells. Anat Rec 196:263–273. https://doi.org/10.1002/ar.1091960302

    Article  CAS  PubMed  Google Scholar 

  62. Francis JC, Swain A (2018) Prostate organogenesis. Cold Spring Harb Perspect Med. https://doi.org/10.1101/cshperspect.a030353

    Article  PubMed  PubMed Central  Google Scholar 

  63. Timms BG (2008) Prostate development: a historical perspective. Differentiation 76:565–577. https://doi.org/10.1111/j.1432-0436.2008.00278.x

    Article  CAS  PubMed  Google Scholar 

  64. Quick CM, Gokden N, Sangoi AR et al (2010) The distribution of PAX-2 immunoreactivity in the prostate gland, seminal vesicle, and ejaculatory duct: comparison with prostatic adenocarcinoma and discussion of prostatic zonal embryogenesis. Hum Pathol 41:1145–1149. https://doi.org/10.1016/j.humpath.2010.01.010

    Article  CAS  PubMed  Google Scholar 

  65. Cunha GR, Vezina CM, Isaacson D et al (2018) Development of the human prostate. Differentiation 103:24–45. https://doi.org/10.1016/j.diff.2018.08.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Deb S, Chin MY, Pham S et al (2021) Steroidogenesis in peripheral and transition zones of human prostate cancer tissue. Int J Mol Sci. https://doi.org/10.3390/ijms22020487

    Article  PubMed  PubMed Central  Google Scholar 

  67. Frick J, Aulitzky W (1991) Physiology of the prostate. Infection 19(Suppl 3):S115–S118. https://doi.org/10.1007/BF01643679

    Article  PubMed  Google Scholar 

  68. Zhu Y-S, Imperato-McGinley JL (2009) 5alpha-reductase isozymes and androgen actions in the prostate. Ann N Y Acad Sci 1155:43–56. https://doi.org/10.1111/j.1749-6632.2009.04115.x

    Article  CAS  PubMed  Google Scholar 

  69. Jang Y-G, Go R-E, Hwang K-A et al (2019) Resveratrol inhibits DHT-induced progression of prostate cancer cell line through interfering with the AR and CXCR4 pathway. J Steroid Biochem Mol Biol 192:105406. https://doi.org/10.1016/j.jsbmb.2019.105406

    Article  CAS  PubMed  Google Scholar 

  70. Joseph DB, Henry GH, Malewska A et al (2022) 5-Alpha reductase inhibitors induce a prostate luminal to club cell transition in human benign prostatic hyperplasia. J Pathol 256:427–441. https://doi.org/10.1002/path.5857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Cleutjens KB, van Eekelen CC, van der Korput HA et al (1996) Two androgen response regions cooperate in steroid hormone regulated activity of the prostate-specific antigen promoter. J Biol Chem 271:6379–6388. https://doi.org/10.1074/jbc.271.11.6379

    Article  CAS  PubMed  Google Scholar 

  72. Wilson S, Qi J, Filipp FV (2016) Refinement of the androgen response element based on ChIP-Seq in androgen-insensitive and androgen-responsive prostate cancer cell lines. Sci Rep 6:32611. https://doi.org/10.1038/srep32611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. York TP, Plymate SR, Nelson PS et al (2005) cDNA microarray analysis identifies genes induced in common by peptide growth factors and androgen in human prostate epithelial cells. Mol Carcinog 44:242–251. https://doi.org/10.1002/mc.20139

    Article  CAS  PubMed  Google Scholar 

  74. Feneley MR, Puddefoot JR, Xia S et al (1995) Zonal biochemical and morphological characteristics in BPH. Br J Urol 75:608–613. https://doi.org/10.1111/j.1464-410x.1995.tb07418.x

    Article  CAS  PubMed  Google Scholar 

  75. Jiang Q, Han B-M, Zhao F-J et al (2011) The differential effects of prostate stromal cells derived from different zones on prostate cancer epithelial cells under the action of sex hormones. Asian J Androl 13:798–805. https://doi.org/10.1038/aja.2011.22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported in part by [the Fundamental Research Funds for the Central Universities, Dongzhimen Hospital, Beijing University of Chinese Medicine], [Beijing Traditional Chinese Medicine “Torch Inheritance 3 + 3 Project”-the Wang Pei Famous Doctor Inheritance Workstation—Dongzhimen Hospital Branch], and [the Wu Jie-ping Medical Foundation Special Fund for Young people with TCM dominant diseases],and [Talent development program of Dongzhimen Hospital, Beijing University of Chinese Medicine].

Author information

Author notes

  1. Xu-dong Yu, Shao-shuai Yan and Rui-jia Liu have contributed equally to this work and share the first authorship.

Authors and Affiliations

  1. Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China

    Xu-dong Yu, Shao-shuai Yan, Rui-jia Liu & Yao-sheng Zhang

  2. Beijing Tumour Minimally Invasive Medical Center of Integrated Traditional Chinese and Western Medicine, Beijing, China

    Xu-dong Yu & Yao-sheng Zhang

Authors
  1. Xu-dong Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shao-shuai Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rui-jia Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yao-sheng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yao-sheng Zhang.

Ethics declarations

Conflict of interest

All the authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yu, Xd., Yan, Ss., Liu, Rj. et al. Apparent differences in prostate zones: susceptibility to prostate cancer, benign prostatic hyperplasia and prostatitis. Int Urol Nephrol (2024). https://doi.org/10.1007/s11255-024-04012-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11255-024-04012-w

Keywords

Search

Navigation