Korean J Urol.  2012 May;53(5):297-303.

High-Grade Prostatic Intraepithelial Neoplasia

• Klink JC
• Miocinovic R
• Magi Galluzzi C
• Klein EA

Abstract

High-grade prostatic intraepithelial neoplasia (HGPIN) has been established as a precursor to prostatic adenocarcinoma. HGPIN shares many morphological, genetic, and molecular signatures with prostate cancer. Its predictive value for the development of future adenocarcinoma during the prostate-specific antigen screening era has decreased, mostly owing to the increase in prostate biopsy cores. Nevertheless, a literature review supports that large-volume HGPIN and multiple cores of involvement at the initial biopsy should prompt a repeat biopsy of the prostate within 1 year. No treatment is recommended for HGPIN to slow its progression to cancer.

Keyword

HGPIN; High grade prostatic intraepithelial neoplasia; Prostate biopsy; Prostate cancer

MeSH Terms

Adenocarcinoma
Biopsy
Mass Screening
Prostate
Prostate-Specific Antigen
Prostatic Intraepithelial Neoplasia
Prostatic Neoplasms
Prostate-Specific Antigen

Figure

• 

  FIG. 1 Prostatic gland with HGPIN (right) and normal prostatic gland (left). Note the preserved architecture of the gland involved by HGPIN and largely intact basal cell layer (H&E, ×20). HGPIN, high-grade prostatic intraepithelial neoplasia.

• 

  FIG. 2 High-power view of prostatic gland with HGPIN showing enlarged secretory cells with increased nuclear/cytoplasmic ratio and prominent nucleoli. Note the partially disrupted basal cell layer (H&E, ×40). HGPIN, high-grade prostatic intraepithelial neoplasia.

Reference

1. Epstein JI, Grignon DJ, Humphrey PA, McNeal JE, Sesterhenn IA, Troncoso P, et al. Interobserver reproducibility in the diagnosis of prostatic intraepithelial neoplasia. Am J Surg Pathol. 1995. 19:873–886.

2. McNeal JE, Bostwick DG. Intraductal dysplasia: a premalignant lesion of the prostate. Hum Pathol. 1986. 17:64–71.

3. Allam CK, Bostwick DG, Hayes JA, Upton MP, Wade GG, Domanowski GF, et al. Interobserver variability in the diagnosis of high-grade prostatic intraepithelial neoplasia and adenocarcinoma. Mod Pathol. 1996. 9:742–751.

4. Bostwick DG, Cheng L. Precursors of prostate cancer. Histopathology. 2012. 60:4–27.

5. Guzzo TJ, Kutikov A, Canter DJ, Tomaszewski JE, Magerfleish L, VanArsdalen K, et al. The clinical and pathological history of prostate cancer progression in men with a prior history of high grade prostatic intraepithelial neoplasia. Can J Urol. 2008. 15:4174–4178.

6. Lefkowitz GK, Taneja SS, Brown J, Melamed J, Lepor H. Followup interval prostate biopsy 3 years after diagnosis of high grade prostatic intraepithelial neoplasia is associated with high likelihood of prostate cancer, independent of change in prostate specific antigen levels. J Urol. 2002. 168:1415–1418.

7. Antonelli A, Tardanico R, Giovanessi L, Pesenti N, Gatti L, Zambolin T, et al. Predicting prostate cancer at rebiopsies in patients with high-grade prostatic intraepithelial neoplasia: a study on 546 patients. Prostate Cancer Prostatic Dis. 2011. 14:173–176.

8. Bostwick DG. Prospective origins of prostate carcinoma. Prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia. Cancer. 1996. 78:330–336.

9. Häggman MJ, Macoska JA, Wojno KJ, Oesterling JE. The relationship between prostatic intraepithelial neoplasia and prostate cancer: critical issues. J Urol. 1997. 158:12–22.

10. 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.

11. Abdel-Khalek M, El-Baz M, Ibrahiem el-H. Predictors of prostate cancer on extended biopsy in patients with high-grade prostatic intraepithelial neoplasia: a multivariate analysis model. BJU Int. 2004. 94:528–533.

12. Roscigno M, Scattoni V, Freschi M, Raber M, Colombo R, Bertini R, et al. Monofocal and plurifocal high-grade prostatic intraepithelial neoplasia on extended prostate biopsies: factors predicting cancer detection on extended repeat biopsy. Urology. 2004. 63:1105–1110.

13. Kronz JD, Allan CH, Shaikh AA, Epstein JI. Predicting cancer following a diagnosis of high-grade prostatic intraepithelial neoplasia on needle biopsy: data on men with more than one follow-up biopsy. Am J Surg Pathol. 2001. 25:1079–1085.

14. Cerveira N, Ribeiro FR, Peixoto A, Costa V, Henrique R, Jerónimo C, et al. TMPRSS2-ERG gene fusion causing ERG overexpression precedes chromosome copy number changes in prostate carcinomas and paired HGPIN lesions. Neoplasia. 2006. 8:826–832.

15. Perner S, Mosquera JM, Demichelis F, Hofer MD, Paris PL, Simko J, et al. TMPRSS2-ERG fusion prostate cancer: an early molecular event associated with invasion. Am J Surg Pathol. 2007. 31:882–888.

16. Sakr WA, Grignon DJ, Haas GP, Heilbrun LK, Pontes JE, Crissman JD. Age and racial distribution of prostatic intraepithelial neoplasia. Eur Urol. 1996. 30:138–144.

17. Sakr WA, Grignon DJ, Haas GP. Pathology of premalignant lesions and carcinoma of the prostate in African-American men. Semin Urol Oncol. 1998. 16:214–220.

18. Epstein JI, Herawi M. Prostate needle biopsies containing prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma: implications for patient care. J Urol. 2006. 175:820–834.

19. Zynger DL, Yang X. High-grade prostatic intraepithelial neoplasia of the prostate: the precursor lesion of prostate cancer. Int J Clin Exp Pathol. 2009. 2:327–338.

20. Han KS, Jeong IG, Joung JY, Yang SO, Chung J, Seo HK, et al. Prevalence of high-grade prostatic intraepithelial neoplasia in prostate gland of Korean men: comparisons between radical prostatectomy and cystoprostatectomy. Urology. 2007. 70:1100–1103.

21. Tan PH, Tan HW, Tan Y, Lim CN, Cheng C, Epstein JI, et al. Is high-grade prostatic intraepithelial neoplasia on needle biopsy different in an Asian population: a clinicopathologic study performed in Singapore. Urology. 2006. 68:800–803.

22. Weinstein MH, Epstein JI. Significance of high-grade prostatic intraepithelial neoplasia on needle biopsy. Hum Pathol. 1993. 24:624–629.

23. Keetch DW, Humphrey P, Stahl D, Smith DS, Catalona WJ. Morphometric analysis and clinical followup of isolated prostatic intraepithelial neoplasia in needle biopsy of the prostate. J Urol. 1995. 154:347–351.

24. Park S, Shinohara K, Grossfeld GD, Carroll PR. Prostate cancer detection in men with prior high grade prostatic intraepithelial neoplasia or atypical prostate biopsy. J Urol. 2001. 165:1409–1414.

25. Bostwick DG, Qian J. High-grade prostatic intraepithelial neoplasia. Mod Pathol. 2004. 17:360–379.

26. Emmert-Buck MR, Vocke CD, Pozzatti RO, Duray PH, Jennings SB, Florence CD, et al. Allelic loss on chromosome 8p12-21 in microdissected prostatic intraepithelial neoplasia. Cancer Res. 1995. 55:2959–2962.

27. Miet SM, Neyra M, Jaques R, Dubernard P, Revol AA, Marçais C. RER(+) phenotype in prostate intra-epithelial neoplasia associated with human prostate-carcinoma development. Int J Cancer. 1999. 82:635–639.

28. Baltaci S, Orhan D, Ozer G, Tolunay O, Gögõüs O. Bcl-2 proto-oncogene expression in low- and high-grade prostatic intraepithelial neoplasia. BJU Int. 2000. 85:155–159.

29. Qian J, Bostwick DG, Takahashi S, Borell TJ, Herath JF, Lieber MM, et al. Chromosomal anomalies in prostatic intraepithelial neoplasia and carcinoma detected by fluorescence in situ hybridization. Cancer Res. 1995. 55:5408–5414.

30. Willman JH, Holden JA. Immunohistochemical staining for DNA topoisomerase II-alpha in benign, premalignant, and malignant lesions of the prostate. Prostate. 2000. 42:280–286.

31. Ge K, Minhas F, Duhadaway J, Mao NC, Wilson D, Buccafusca R, et al. Loss of heterozygosity and tumor suppressor activity of Bin1 in prostate carcinoma. Int J Cancer. 2000. 86:155–161.

32. Koeneman KS, Pan CX, Jin JK, Pyle JM 3rd, Flanigan RC, Shankey TV, et al. Telomerase activity, telomere length, and DNA ploidy in prostatic intraepithelial neoplasia (PIN). J Urol. 1998. 160:1533–1539.

33. Mosquera JM, Perner S, Genega EM, Sanda M, Hofer MD, Mertz KD, et al. Characterization of TMPRSS2-ERG fusion high-grade prostatic intraepithelial neoplasia and potential clinical implications. Clin Cancer Res. 2008. 14:3380–3385.

34. Bostwick DG, Pacelli A, Lopez-Beltran A. Molecular biology of prostatic intraepithelial neoplasia. Prostate. 1996. 29:117–134.

35. Montironi R, Mazzucchelli R, Lopez-Beltran A, Scarpelli M, Cheng L. Prostatic intraepithelial neoplasia: its morphological and molecular diagnosis and clinical significance. BJU Int. 2011. 108:1394–1401.

36. Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005. 310:644–648.

37. Attard G, Clark J, Ambroisine L, Fisher G, Kovacs G, Flohr P, et al. Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. Oncogene. 2008. 27:253–263.

38. Perner S, Demichelis F, Beroukhim R, Schmidt FH, Mosquera JM, Setlur S, et al. TMPRSS2:ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. Cancer Res. 2006. 66:8337–8341.

39. Gopalan A, Leversha MA, Satagopan JM, Zhou Q, Al-Ahmadie HA, Fine SW, et al. TMPRSS2-ERG gene fusion is not associated with outcome in patients treated by prostatectomy. Cancer Res. 2009. 69:1400–1406.

40. Morote J, Fernández S, Alaña L, Iglesias C, Planas J, Reventós J, et al. PTOV1 expression predicts prostate cancer in men with isolated high-grade prostatic intraepithelial neoplasia in needle biopsy. Clin Cancer Res. 2008. 14:2617–2622.

41. Evren S, Dermen A, Lockwood G, Fleshner N, Sweet J. mTOR-RAPTOR and 14-3-3sigma immunohistochemical expression in high grade prostatic intraepithelial neoplasia and prostatic adenocarcinomas: a tissue microarray study. J Clin Pathol. 2011. 64:683–688.

42. Swinnen JV, Roskams T, Joniau S, Van Poppel H, Oyen R, Baert L, et al. Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer. Int J Cancer. 2002. 98:19–22.

43. Yasunaga Y, Shin M, Fujita MQ, Nonomura N, Miki T, Okuyama A, et al. Different patterns of p53 mutations in prostatic intraepithelial neoplasia and concurrent carcinoma: analysis of microdissected specimens. Lab Invest. 1998. 78:1275–1279.

44. Brooks JD, Weinstein M, Lin X, Sun Y, Pin SS, Bova GS, et al. CG island methylation changes near the GSTP1 gene in prostatic intraepithelial neoplasia. Cancer Epidemiol Biomarkers Prev. 1998. 7:531–536.

45. Bostwick DG, Brawer MK. Prostatic intra-epithelial neoplasia and early invasion in prostate cancer. Cancer. 1987. 59:788–794.

46. Bostwick DG, Amin MB, Dundore P, Marsh W, Schultz DS. Architectural patterns of high-grade prostatic intraepithelial neoplasia. Hum Pathol. 1993. 24:298–310.

47. Schlesinger C, Bostwick DG, Iczkowski KA. High-grade prostatic intraepithelial neoplasia and atypical small acinar proliferation: predictive value for cancer in current practice. Am J Surg Pathol. 2005. 29:1201–1207.

48. Bostwick DG, Cheng L. Precursors of prostate cancer. Histopathology. 2012. 60:4–27.

49. Herawi M, Kahane H, Cavallo C, Epstein JI. Risk of prostate cancer on first re-biopsy within 1 year following a diagnosis of high grade prostatic intraepithelial neoplasia is related to the number of cores sampled. J Urol. 2006. 175:121–124.

50. Eskicorapci SY, Guliyev F, Islamoglu E, Ergen A, Ozen H. The effect of prior biopsy scheme on prostate cancer detection for repeat biopsy population: results of the 14-core prostate biopsy technique. Int Urol Nephrol. 2007. 39:189–195.

51. Lee MC, Moussa AS, Zaytoun O, Yu C, Jones JS. Using a saturation biopsy scheme increases cancer detection during repeat biopsy in men with high-grade prostatic intra-epithelial neoplasia. Urology. 2011. 78:1115–1119.

52. Rabets JC, Jones JS, Patel A, Zippe CD. Prostate cancer detection with office based saturation biopsy in a repeat biopsy population. J Urol. 2004. 172:94–97.

53. Roscigno M, Scattoni V, Freschi M, Abdollah F, Maccagnano C, Galosi A, et al. Diagnosis of isolated high-grade prostatic intra-epithelial neoplasia: proposal of a nomogram for the prediction of cancer detection at saturation re-biopsy. BJU Int. 2011. Epub ahead of print.

54. Akhavan A, Keith JD, Bastacky SI, Cai C, Wang Y, Nelson JB. The proportion of cores with high-grade prostatic intraepithelial neoplasia on extended-pattern needle biopsy is significantly associated with prostate cancer on site-directed repeat biopsy. BJU Int. 2007. 99:765–769.

55. Heidenreich A, Bellmunt J, Bolla M, Joniau S, Mason M, Matveev V, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Eur Urol. 2011. 59:61–71.

56. Kawachi MH, Bahnson RR, Barry M, Busby JE, Carroll PR, Carter HB, et al. NCCN clinical practice guidelines in oncology: prostate cancer early detection. J Natl Compr Canc Netw. 2010. 8:240–262.

57. Gallo F, Chiono L, Gastaldi E, Venturino E, Giberti C. Prognostic significance of high-grade prostatic intraepithelial neoplasia (HGPIN): risk of prostatic cancer on repeat biopsies. Urology. 2008. 72:628–632.

58. Thompson IM, Lucia MS, Redman MW, Darke A, La Rosa FG, Parnes HL, et al. Finasteride decreases the risk of prostatic intraepithelial neoplasia. J Urol. 2007. 178:107–109.

59. Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010. 362:1192–1202.

60. Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G, Corti A. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res. 2006. 66:1234–1240.

61. Fleshner NE, Kapusta L, Donnelly B, Tanguay S, Chin J, Hersey K, et al. Progression from high-grade prostatic intraepithelial neoplasia to cancer: a randomized trial of combination vitamin-E, soy, and selenium. J Clin Oncol. 2011. 29:2386–2390.

62. Lefkowitz GK, Sidhu GS, Torre P, Lepor H, Taneja SS. Is repeat prostate biopsy for high-grade prostatic intraepithelial neoplasia necessary after routine 12-core sampling? Urology. 2001. 58:999–1003.

63. Moore CK, Karikehalli S, Nazeer T, Fisher HA, Kaufman RP Jr, Mian BM. Prognostic significance of high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation in the contemporary era. J Urol. 2005. 173:70–72.

64. Schoenfield L, Jones JS, Zippe CD, Reuther AM, Klein E, Zhou M, et al. The incidence of high-grade prostatic intraepithelial neoplasia and atypical glands suspicious for carcinoma on first-time saturation needle biopsy, and the subsequent risk of cancer. BJU Int. 2007. 99:770–774.

65. De Nunzio C, Trucchi A, Miano R, Stoppacciaro A, Fattahi H, Cicione A, et al. The number of cores positive for high grade prostatic intraepithelial neoplasia on initial biopsy is associated with prostate cancer on second biopsy. J Urol. 2009. 181:1069–1074.

66. Antonelli A, Tardanico R, Giovanessi L, Pesenti N, Gatti L, Zambolin T, et al. Predicting prostate cancer at rebiopsies in patients with high-grade prostatic intraepithelial neoplasia: a study on 546 patients. Prostate Cancer Prostatic Dis. 2011. 14:173–176.

67. Bishara T, Ramnani DM, Epstein JI. High-grade prostatic intraepithelial neoplasia on needle biopsy: risk of cancer on repeat biopsy related to number of involved cores and morphologic pattern. Am J Surg Pathol. 2004. 28:629–633.

68. Netto GJ, Epstein JI. Widespread high-grade prostatic intraepithelial neoplasia on prostatic needle biopsy: a significant likelihood of subsequently diagnosed adenocarcinoma. Am J Surg Pathol. 2006. 30:1184–1188.