Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. X:X | DOI: 10.5507/bp.2025.003

Contemporary review of prognostic markers of prostate cancer from a pathologist perspective

Martin Elias1, Jan Bouchal1, Milan Kral2, Daniela Kurfurstova1
1 Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic
2 Department of Urology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic

Prostate cancer is the most frequently diagnosed malignant tumour in men worldwide. To treat this condition, prognostic markers to distinguish indolent from aggressive disease, and biomarkers for metastatic forms are needed. From a pathologist's perspective, despite the plethora of emerging biomarkers, none to date has made its way into clinical practice. The need for prognostic and predictive markers following histological evaluation remains. This overview of some putative immunohistochemical and genetic markers reveals the pitfalls of biomarker research, notably verifiability, validity and interlaboratory comparison. Meta-analyses and extensive cooperation between pathology departments are a sine qua non. Codes of Best Practice such as the REMARK guidelines have been advocated as a path forward. Currently, the most widely used and validated prognostic marker remains the Gleason score. Ki67 along with PTEN are the most promising prognostic markers.

Keywords: prostate adenocarcinoma, Gleason score, prostate biopsy, radical prostatectomy, immunohistochemistry, prognostic and predictive markers

Received: October 2, 2024; Revised: November 8, 2024; Accepted: January 22, 2025; Prepublished online: February 5, 2025 

Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Novotvary 2011-2021. Zdravotnická statistika ČR. Ústav zdravotnických informací a statistiky ČR. [cited 2024 March 1] Available from: https://www.uzis.cz/res/f/008447/novotvary2019-2021.pdf (In Czech)
    2. Culp MB, Soerjomataram I, Efstathiou JA, Bray F, Jemal A. Recent Global Patterns in Prostate Cancer Incidence and Mortality Rates. Eur Urol 2020;77(1):38-52. doi: 10.1016/j.eururo.2019.08.005 Go to original source... Go to PubMed...
    3. Thomsen FB, Brasso K, Klotz LH, Røder MA, Berg KD, Iversen P. Active surveillance for clinically localized prostate cancer--a systematic review. J Surg Oncol 2014;109(8):830-5. doi: 10.1002/jso.23584 Go to original source... Go to PubMed...
    4. Navarro-Pelayo Láinez MM, Rodríguez-Fernández A, Gómez-Río M, Vázquez-Alonso F, Cózar-Olmo JM, Llamas-Elvira JM. The role of positron emission tomography/computed tomography imaging with radiolabeled choline analogues in prostate cancer. Actas Urol Esp 2014;38(9):613-21. English, Spanish. doi: 10.1016/j.acuro.2013.12.008 Go to original source... Go to PubMed...
    5. Morote J, Aguilar A, Planas J, Trilla E. Definition of Castrate Resistant Prostate Cancer: New Insights. Biomedicines 2022;10(3):689. doi: 10.3390/biomedicines10030689 Go to original source... Go to PubMed...
    6. Kurfürstová D, Král M. Adenokarcinom prostaty a hodnocení stupně jeho diferenciace: změny v hodnocení Gleasonova skóre od jeho vzniku po současnost a jeho význam pro praxi patologa a urologa. Urologie pro praxi 2013;14(4):157-9. (In Czech)
    7. Shah RB, Zhou M. Recent advances in prostate cancer pathology: Gleason grading and beyond. Pathol Int 2016;66(5):260-72. doi: 10.1111/pin.12398 Go to original source... Go to PubMed...
    8. WHO Classification of Tumours Editorial Board. Urinary and Male Genital Tumours. 5th ed. Lyon, France: International Agency for Research on Cancer; 2022.
    9. Mejak SL, Bayliss J, Hanks SD. Long distance bicycle riding causes prostate-specific antigen to increase in men aged 50 years and over. PLoS One 2013;8(2):e56030. doi: 10.1371/journal.pone.0056030 Go to original source... Go to PubMed...
    10. Bonk S, Kluth M, Hube-Magg C, Polonski A, Soekeland G, Makropidi-Fraune G, Möller-Koop C, Witt M, Luebke AM, Hinsch A, Burandt E, Steurer S, Clauditz TS, Schlomm T, Perez D, Graefen M, Heinzer H, Huland H, Izbicki JR, Wilczak W, Minner S, Sauter G, Simon R. Prognostic and diagnostic role of PSA immunohistochemistry: A tissue microarray study on 21,000 normal and cancerous tissues. Oncotarget 2019;10(52):5439-53. doi: 10.18632/oncotarget.27145 Go to original source... Go to PubMed...
    11. Moradi A, Srinivasan S, Clements J, Batra J. Beyond the biomarker role: prostate-specific antigen (PSA) in the prostate cancer microenvironment. Cancer Metastasis Rev 2019;38(3):333-46. doi: 10.1007/s10555-019-09815-3 Go to original source... Go to PubMed...
    12. Vik V, ©ácha P, Koukolík F, Konvalinka J, Pacík D, Zachoval R. Co nového víme o PSMA (prostatický specifický membránový antigen) z pohledu urologa. Urologické listy 2007;6(4):10-13. (In Czech)
    13. Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, Bolton D, Lawrentschuk N. Sensitivity, Specificity, and Predictors of Positive 68Ga-Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol 2016;70(6):926-37. doi: 10.1016/j.eururo.2016.06.021 Go to original source... Go to PubMed...
    14. von Eyben FE, Roviello G, Kiljunen T, Uprimny C, Virgolini I, Kairemo K, Joensuu T. Third-line treatment and 177Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review. Eur J Nucl Med Mol Imaging 2018;45(3):496-508. doi: 10.1007/s00259-017-3895-x Go to original source... Go to PubMed...
    15. Reissig F, Zarschler K, Novy Z, Petrik M, Bendova K, Kurfurstova D, Bouchal J, Ludik MC, Brandt F, Kopka K, Khoylou M, Pietzsch HJ, Hajduch M, Mamat C. Modulating the pharmacokinetic profile of Actinium-225-labeled macropa-derived radioconjugates by dual targeting of PSMA and albumin. Theranostics 2022;12(17):7203-15. doi: 10.7150/thno.78043 Go to original source... Go to PubMed...
    16. Fantony JJ, Howard LE, Csizmadi I, Armstrong AJ, Lark AL, Galet C, Aronson WJ, Freedland SJ. Is Ki67 prognostic for aggressive prostate cancer? A multicenter real-world study. Biomark Med 2018;12(7):727-36. doi: 10.2217/bmm-2017-0322 Go to original source... Go to PubMed...
    17. Tretiakova MS, Wei W, Boyer HD, Newcomb LF, Hawley S, Auman H, Vakar-Lopez F, McKenney JK, Fazli L, Simko J, Troyer DA, Hurtado-Coll A, Thompson IM Jr, Carroll PR, Ellis WJ, Gleave ME, Nelson PS, Lin DW, True LD, Feng Z, Brooks JD. Prognostic value of Ki67 in localized prostate carcinoma: a multi-institutional study of >1000 prostatectomies. Prostate Cancer Prostatic Dis 2016;19(3):264-70. doi: 10.1038/pcan.2016.12 Go to original source... Go to PubMed...
    18. Mathieu R, Shariat SF, Seitz C, Karakiewicz PI, Fajkovic H, Sun M, Lotan Y, Scherr DS, Tewari A, Montorsi F, Briganti A, Rouprêt M, Lucca I, Margulis V, Rink M, Kluth LA, Rieken M, Bachman A, Xylinas E, Robinson BD, Bensalah K, Margreiter M. Multi-institutional validation of the prognostic value of Ki-67 labeling index in patients treated with radical prostatectomy. World J Urol 2015;33(8):1165-71. doi: 10.1007/s00345-014-1421-3 Go to original source... Go to PubMed...
    19. Kristiansen G. Diagnostic and prognostic molecular biomarkers for prostate cancer. Histopathology 2012;60(1):125-41. doi: 10.1111/j.1365-2559.2011.04083.x Go to original source... Go to PubMed...
    20. Lin H, Liu Q, Zeng X, Yu W, Xu G. Pembrolizumab with or without enzalutamide in selected populations of men with previously untreated metastatic castration-resistant prostate cancer harbouring programmed cell death ligand-1 staining: a retrospective study. BMC Cancer 2021;21(1):399. doi: 10.1186/s12885-021-08156-1 Go to original source... Go to PubMed...
    21. Shen H, Liu J, Sun G, Yan L, Li Q, Wang Z, Xie L. The clinicopathological significance and prognostic value of programmed death-ligand 1 in prostate cancer: a meta-analysis of 3133 patients. Aging (Albany NY). 2020;13(2):2279-93. doi: 10.18632/aging.202248 Go to original source... Go to PubMed...
    22. He J, Yi M, Tan L, Huang J, Huang L. The immune checkpoint regulator PD-L1 expression are associated with clinical progression in prostate cancer. World J Surg Oncol 2021;19(1):215. doi: 10.1186/s12957-021-02325-z Go to original source... Go to PubMed...
    23. Ruiz de Porras V, Pardo JC, Notario L, Etxaniz O, Font A. Immune Checkpoint Inhibitors: A Promising Treatment Option for Metastatic Castration-Resistant Prostate Cancer? Int J Mol Sci 2021;22(9):4712. doi: 10.3390/ijms22094712 Go to original source... Go to PubMed...
    24. Schepisi G, Brighi N, Cursano MC, Gurioli G, Ravaglia G, Altavilla A, Burgio SL, Testoni S, Menna C, Farolfi A, Casadei C, Tonini G, Santini D, De Giorgi U. Inflammatory Biomarkers as Predictors of Response to Immunotherapy in Urological Tumors. J Oncol 2019;2019:7317964. doi: 10.1155/2019/7317964 Go to original source... Go to PubMed...
    25. Shim KH, Kwon JE, Park SG, Choo SH, Kim SJ, Kim SI. Cell membrane and nuclear expression of programmed death ligand-1 in prostate needle biopsy tissue in prostate cancer patients undergoing primary radiation therapy. Urol Oncol 2021;39(5):298.e13-298.e20. doi: 10.1016/j.urolonc.2021.01.032 Go to original source... Go to PubMed...
    26. Becker F, Joerg V, Hupe MC, Roth D, Krupar R, Lubczyk V, Kuefer R, Sailer V, Duensing S, Kirfel J, Merseburger AS, Brägelmann J, Perner S, Offermann A. Increased mediator complex subunit CDK19 expression associates with aggressive prostate cancer. Int J Cancer 2020;146(2):577-88. doi: 10.1002/ijc.32551 Go to original source... Go to PubMed...
    27. Li J, Davidson D, Martins Souza C, Zhong MC, Wu N, Park M, Muller WJ, Veillette A. Loss of PTPN12 Stimulates Progression of ErbB2-Dependent Breast Cancer by Enhancing Cell Survival, Migration, and Epithelial-to-Mesenchymal Transition. Mol Cell Biol 2015;35(23):4069-82. doi: 10.1128/MCB.00741-15 Go to original source... Go to PubMed...
    28. Weidemann SA, Sauer C, Luebke AM, Möller-Koop C, Steurer S, Hube-Magg C, Büscheck F, Höflmayer D, Tsourlakis MC, Clauditz TS, Simon R, Sauter G, Göbel C, Lebok P, Dum D, Fraune C, Kind S, Minner S, Izbicki J, Schlomm T, Huland H, Heinzer H, Burandt E, Haese A, Graefen M, Heumann A. High-level expression of protein tyrosine phosphatase non-receptor 12 is a strong and independent predictor of poor prognosis in prostate cancer. BMC Cancer 2019;19(1):944. doi: 10.1186/s12885-019-6182-3 Go to original source... Go to PubMed...
    29. Viré E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, Morey L, Van Eynde A, Bernard D, Vanderwinden JM, Bollen M, Esteller M, Di Croce L, de Launoit Y, Fuks F. The Polycomb group protein EZH2 directly controls DNA methylation. Nature 2006;439(7078):871-4. doi: 10.1038/nature04431 Go to original source... Go to PubMed...
    30. Abdelrahman AE, Arafa SA, Ahmed RA. Prognostic Value of Twist-1, E-cadherin and EZH2 in Prostate Cancer: An Immunohistochemical Study. Turk Patoloji Derg 2017;1(1):198-210. English. doi: 10.5146/tjpath.2016.01392 Go to original source... Go to PubMed...
    31. Xin L. EZH2 accompanies prostate cancer progression. Nat Cell Biol 2021;23(9):934-36. doi: 10.1038/s41556-021-00744-4 Go to original source... Go to PubMed...
    32. Rubin MA, Mucci NR, Figurski J, Fecko A, Pienta KJ, Day ML. E-cadherin expression in prostate cancer: a broad survey using high-density tissue microarray technology. Hum Pathol 2001;32(7):690-7. doi: 10.1053/hupa.2001.25902 Go to original source... Go to PubMed...
    33. Huber F, Montani M, Sulser T, Jaggi R, Wild P, Moch H, Gevensleben H, Schmid M, Wyder S, Kristiansen G. Comprehensive validation of published immunohistochemical prognostic biomarkers of prostate cancer -what has gone wrong? A blueprint for the way forward in biomarker studies. Br J Cancer 2015;112(1):140-8. doi: 10.1038/bjc.2014.588 Go to original source... Go to PubMed...
    34. Sauerbrei W, Taube SE, McShane LM, Cavenagh MM, Altman DG. Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): An Abridged Explanation and Elaboration. J Natl Cancer Inst 2018;110(8):803-11. doi: 10.1093/jnci/djy088 Go to original source... Go to PubMed...
    35. Arora K, Barbieri CE. Molecular Subtypes of Prostate Cancer. Curr Oncol Rep 2018;20(8):58. doi: 10.1007/s11912-018-0707-9 Go to original source... Go to PubMed...
    36. Wei T, Lu J, Ma T, Huang H, Kocher JP, Wang L. Re-Evaluate Fusion Genes in Prostate Cancer. Cancer Inform 2021;20:11769351211027592. doi: 10.1177/11769351211027592 Go to original source... Go to PubMed...
    37. Cancer Genome Atlas Research Network. The Molecular Taxonomy of Primary Prostate Cancer. Cell 2015;163(4):1011-25. doi: 10.1016/j.cell.2015.10.025 Go to original source... Go to PubMed...
    38. Kobelyatskaya AA, Pudova EA, Snezhkina AV, Fedorova MS, Pavlov VS, Guvatova ZG, Savvateeva MV, Melnikova NV, Dmitriev AA, Trofimov DY, Sukhikh GT, Nyushko KM, Alekseev BY, Razin SV, Krasnov GS, Kudryavtseva AV. Impact TMPRSS2-ERG Molecular Subtype on Prostate Cancer Recurrence. Life (Basel) 2021;11(6):588. doi: 10.3390/life11060588 Go to original source... Go to PubMed...
    39. Oikawa T, Yamada T. Molecular biology of the Ets family of transcription factors. Gene 2003;303:11-34. doi: 10.1016/s0378-1119(02)01156-3 Go to original source... Go to PubMed...
    40. Chalmers ZR, Burns MC, Ebot EM, Frampton GM, Ross JS, Hussain MHA, Abdulkadir SA. Early-onset metastatic and clinically advanced prostate cancer is a distinct clinical and molecular entity characterized by increased TMPRSS2-ERG fusions. Prostate Cancer Prostatic Dis 2021;24(2):558-66. doi: 10.1038/s41391-020-00314-z Go to original source... Go to PubMed...
    41. Park K, Tomlins SA, Mudaliar KM, Chiu YL, Esgueva R, Mehra R, Suleman K, Varambally S, Brenner JC, MacDonald T, Srivastava A, Tewari AK, Sathyanarayana U, Nagy D, Pestano G, Kunju LP, Demichelis F, Chinnaiyan AM, Rubin MA. Antibody-based detection of ERG rearrangement-positive prostate cancer. Neoplasia 2010;12(7):590-8. doi: 10.1593/neo.10726 Go to original source... Go to PubMed...
    42. van Leenders GJ, Boormans JL, Vissers CJ, Hoogland AM, Bressers AA, Furusato B, Trapman J. Antibody EPR3864 is specific for ERG genomic fusions in prostate cancer: implications for pathological practice. Mod Pathol 2011;24(8):1128-38. doi: 10.1038/modpathol.2011.65 Go to original source... Go to PubMed...
    43. Shrestha E, Coulter JB, Guzman W, Ozbek B, Hess MM, Mummert L, Ernst SE, Maynard JP, Meeker AK, Heaphy CM, Haffner MC, De Marzo AM, Sfanos KS. Oncogenic gene fusions in nonneoplastic precursors as evidence that bacterial infection can initiate prostate cancer. Proc Natl Acad Sci U S A 2021;118(32):e2018976118. doi: 10.1073/pnas.2018976118 Go to original source... Go to PubMed...
    44. Ugge H, Udumyan R, Carlsson J, Andrén O, Montgomery S, Davidsson S, Fall K. Acne in late adolescence and risk of prostate cancer. Int J Cancer 2018;142(8):1580-5. doi: 10.1002/ijc.31192 Go to original source... Go to PubMed...
    45. Bernasocchi T, Theurillat JP. SPOP-mutant prostate cancer: Translating fundamental biology into patient care. Cancer Lett 2022;529:11-18. doi: 10.1016/j.canlet.2021.12.024 Go to original source... Go to PubMed...
    46. Barbieri CE, Baca SC, Lawrence MS, Demichelis F, Blattner M, Theurillat JP, White TA, Stojanov P, Van Allen E, Stransky N, Nickerson E, Chae SS, Boysen G, Auclair D, Onofrio RC, Park K, Kitabayashi N, MacDonald TY, Sheikh K, Vuong T, Guiducci C, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Hussain WM, Ramos AH, Winckler W, Redman MC, Ardlie K, Tewari AK, Mosquera JM, Rupp N, Wild PJ, Moch H, Morrissey C, Nelson PS, Kantoff PW, Gabriel SB, Golub TR, Meyerson M, Lander ES, Getz G, Rubin MA, Garraway LA. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat Genet 2012;44(6):685-9. doi: 10.1038/ng.2279 Go to original source... Go to PubMed...
    47. Li H, Gigi L, Zhao D. CHD1, a multifaceted epigenetic remodeler in prostate cancer. Front Oncol 2023;13:1123362. doi: 10.3389/fonc.2023.1123362 Go to original source... Go to PubMed...
    48. Jamaspishvili T, Patel PG, Niu Y, Vidotto T, Caven I, Livergant R, Fu W, Kawashima A, How N, Okello JB, Guedes LB, Ouellet V, Picanço C, Koti M, Reis RB, Saad F, Mes-Masson AM, Lotan TL, Squire JA, Peng YP, Siemens DR, Berman DM. Risk Stratification of Prostate Cancer Through Quantitative Assessment of PTEN Loss (qPTEN). J Natl Cancer Inst 2020;112(11):1098-104. doi: 10.1093/jnci/djaa032 Go to original source... Go to PubMed...
    49. Spieker AJ, Gordetsky JB, Maris AS, Dehan LM, Denney JE, Arnold Egloff SA, Scarpato K, Barocas DA, Giannico GA. PTEN expression and morphological patterns in prostatic adenocarcinoma. Histopathology 2021;79(6):1061-71. doi: 10.1111/his.14531 Go to original source... Go to PubMed...
    50. Gordetsky JB, Schaffer K, Hurley PJ. Current conundrums with cribriform prostate cancer. Histopathology 2022;80(7):1038-40. doi: 10.1111/his.14665 Go to original source... Go to PubMed...
    51. Fontana F, Anselmi M, Limonta P. Exploiting the Metabolic Consequences of PTEN Loss and Akt/Hexokinase 2 Hyperactivation in Prostate Cancer: A New Role for δ-Tocotrienol. Int J Mol Sci 2022;23(9):5269. doi: 10.3390/ijms23095269. Go to original source... Go to PubMed...
    52. Wise HM, Hermida MA, Leslie NR. Prostate cancer, PI3K, PTEN and prognosis. Clin Sci (Lond) 2017;131(3):197-210. doi: 10.1042/CS20160026 Go to original source... Go to PubMed...
    53. Lotan TL, Tomlins SA, Bismar TA, Van der Kwast TH, Grignon D, Egevad L, Kristiansen G, Pritchard CC, Rubin MA, Bubendorf L. Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers. I. Molecular Biomarkers in Prostate Cancer. Am J Surg Pathol 2020;44(7):e15-e29. doi: 10.1097/PAS.0000000000001450 Go to original source... Go to PubMed...
    54. Mateo J, Seed G, Bertan C, Rescigno P, Dolling D, Figueiredo I, Miranda S, Nava Rodrigues D, Gurel B, Clarke M, Atkin M, Chandler R, Messina C, Sumanasuriya S, Bianchini D, Barrero M, Petermolo A, Zafeiriou Z, Fontes M, Perez-Lopez R, Tunariu N, Fulton B, Jones R, McGovern U, Ralph C, Varughese M, Parikh O, Jain S, Elliott T, Sandhu S, Porta N, Hall E, Yuan W, Carreira S, de Bono JS. Genomics of lethal prostate cancer at diagnosis and castration resistance. J Clin Invest 2020;130(4):1743-51. doi: 10.1172/JCI132031 Go to original source... Go to PubMed...
    55. Kurfurstova D, Bartkova J, Vrtel R, Mickova A, Burdova A, Majera D, Mistrik M, Kral M, Santer FR, Bouchal J, Bartek J. DNA damage signalling barrier, oxidative stress and treatment-relevant DNA repair factor alterations during progression of human prostate cancer. Mol Oncol 2016;10(6):879-94. doi: 10.1016/j.molonc.2016.02.005 Go to original source... Go to PubMed...
    56. Kurfürstová D. Význam vybraných proteinů v klinicko-patologickém hodnocení karcinomu prostaty [Disertační práce]. [Olomouc]; 2016. (In Czech)
    57. Armenia J, Wankowicz SAM, Liu D, Gao J, Kundra R, Reznik E, Chatila WK, Chakravarty D, Han GC, Coleman I, Montgomery B, Pritchard C, Morrissey C, Barbieri CE, Beltran H, Sboner A, Zafeiriou Z, Miranda S, Bielski CM, Penson AV, Tolonen C, Huang FW, Robinson D, Wu YM, Lonigro R, Garraway LA, Demichelis F, Kantoff PW, Taplin ME, Abida W, Taylor BS, Scher HI, Nelson PS, de Bono JS, Rubin MA, Sawyers CL, Chinnaiyan AM; PCF/SU2C International Prostate Cancer Dream Team; Schultz N, Van Allen EM. The long tail of oncogenic drivers in prostate cancer. Nat Genet 2018;50(5):645-51. doi: 10.1038/s41588-018-0078-z Erratum in: Nat Genet 2019;51(7):1194. doi: 10.1038/s41588-019-0451-6 Go to original source... Go to PubMed...
    58. Abida W, Cyrta J, Heller G, Prandi D, Armenia J, Coleman I, Cieslik M, Benelli M, Robinson D, Van Allen EM, Sboner A, Fedrizzi T, Mosquera JM, Robinson BD, De Sarkar N, Kunju LP, Tomlins S, Wu YM, Nava Rodrigues D, Loda M, Gopalan A, Reuter VE, Pritchard CC, Mateo J, Bianchini D, Miranda S, Carreira S, Rescigno P, Filipenko J, Vinson J, Montgomery RB, Beltran H, Heath EI, Scher HI, Kantoff PW, Taplin ME, Schultz N, deBono JS, Demichelis F, Nelson PS, Rubin MA, Chinnaiyan AM, Sawyers CL. Genomic correlates of clinical outcome in advanced prostate cancer. Proc Natl Acad Sci U S A 2019;116(23):11428-36. doi: 10.1073/pnas.1902651116 Go to original source... Go to PubMed...
    59. Hamid AA, Gray KP, Shaw G, MacConaill LE, Evan C, Bernard B, Loda M, Corcoran NM, Van Allen EM, Choudhury AD, Sweeney CJ. Compound Genomic Alterations of TP53, PTEN, and RB1 Tumor Suppressors in Localized and Metastatic Prostate Cancer. Eur Urol 2019;76(1):89-97. doi: 10.1016/j.eururo.2018.11.045 Go to original source... Go to PubMed...
    60. Drenth JP, te Morsche R, Jansen JB. Mutations in serine protease inhibitor Kazal type 1 are strongly associated with chronic pancreatitis. Gut 2002;50(5):687-92. doi: 10.1136/gut.50.5.687 Go to original source... Go to PubMed...
    61. Tomlins SA, Rhodes DR, Yu J, Varambally S, Mehra R, Perner S, Demichelis F, Helgeson BE, Laxman B, Morris DS, Cao Q, Cao X, Andrén O, Fall K, Johnson L, Wei JT, Shah RB, Al-Ahmadie H, Eastham JA, Eggener SE, Fine SW, Hotakainen K, Stenman UH, Tsodikov A, Gerald WL, Lilja H, Reuter VE, Kantoff PW, Scardino PT, Rubin MA, Bjartell AS, Chinnaiyan AM. The role of SPINK1 in ETS rearrangement-negative prostate cancers. Cancer Cell 2008;13(6):519-28. doi: 10.1016/j.ccr.2008.04.016 Go to original source... Go to PubMed...
    62. Wang C, Wang L, Su B, Lu N, Song J, Yang X, Fu W, Tan W, Han B. Serine protease inhibitor Kazal type 1 promotes epithelial-mesenchymal transition through EGFR signaling pathway in prostate cancer. Prostate 2014;74(7):689-701. doi: 10.1002/pros.22787 Go to original source... Go to PubMed...
    63. Compérat E, Wasinger G, Oszwald A, Kain R, Cancel-Tassin G, Cussenot O. The Genetic Complexity of Prostate Cancer. Genes (Basel) 2020;11(12):1396. doi: 10.3390/genes11121396 Go to original source... Go to PubMed...
    64. Luo J, Attard G, Balk SP, Bevan C, Burnstein K, Cato L, Cherkasov A, De Bono JS, Dong Y, Gao AC, Gleave M, Heemers H, Kanayama M, Kittler R, Lang JM, Lee RJ, Logothetis CJ, Matusik R, Plymate S, Sawyers CL, Selth LA, Soule H, Tilley W, Weigel NL, Zoubeidi A, Dehm SM, Raj GV. Role of Androgen Receptor Variants in Prostate Cancer: Report from the 2017 Mission Androgen Receptor Variants Meeting. Eur Urol 2018;73(5):715-23. doi: 10.1016/j.eururo.2017.11.038 Go to original source... Go to PubMed...
    65. Messina C, Cattrini C, Soldato D, Vallome G, Caffo O, Castro E, Olmos D, Boccardo F, Zanardi E. BRCA Mutations in Prostate Cancer: Prognostic and Predictive Implications. J Oncol 2020;2020:4986365. doi: 10.1155/2020/4986365 Go to original source... Go to PubMed...
    66. Shah S, Rachmat R, Enyioma S, Ghose A, Revythis A, Boussios S. BRCA Mutations in Prostate Cancer: Assessment, Implications and Treatment Considerations. Int J Mol Sci 2021;22(23):12628. doi: 10.3390/ijms222312628 Go to original source... Go to PubMed...
    67. Heidegger I, Kesch C, Kretschmer A, Tsaur I, Ceci F, Valerio M, Tilki D, Marra G, Preisser F, Fankhauser CD, Zattoni F, Chiu P, Puche-Sanz I, Olivier J, van den Bergh RCN, Kasivisvanathan V, Pircher A, Virgolini I, Gandaglia G. Biomarkers to personalize treatment with 177Lu-PSMA-617 in men with metastatic castration-resistant prostate cancer - a state of the art review. Ther Adv Med Oncol 2022;14:17588359221081922. doi: 10.1177/17588359221081922 Go to original source... Go to PubMed...
    68. Nyberg T, Tischkowitz M, Antoniou AC. BRCA1 and BRCA2 pathogenic variants and prostate cancer risk: systematic review and meta-analysis. Br J Cancer 2022;126(7):1067-81. doi: 10.1038/s41416-021-01675-5 Go to original source... Go to PubMed...
    69. Cheng HH, Sokolova AO, Schaeffer EM, Small EJ, Higano CS. Germline and Somatic Mutations in Prostate Cancer for the Clinician. J Natl Compr Canc Netw 2019;17(5):515-21. doi: 10.6004/jnccn.2019.7307 Go to original source... Go to PubMed...
    70. Neeb A, Herranz N, Arce-Gallego S, Miranda S, Buroni L, Yuan W, Athie A, Casals T, Carmichael J, Rodrigues DN, Gurel B, Rescigno P, Rekowski J, Welti J, Riisnaes R, Gil V, Ning J, Wagner V, Casanova-Salas I, Cordoba S, Castro N, Fenor de la Maza MD, Seed G, Chandran K, Ferreira A, Figueiredo I, Bertan C, Bianchini D, Aversa C, Paschalis A, Gonzalez M, Morales-Barrera R, Suarez C, Carles J, Swain A, Sharp A, Gil J, Serra V, Lord C, Carreira S, Mateo J, de Bono JS. Advanced Prostate Cancer with ATM Loss: PARP and ATR Inhibitors. Eur Urol 2021;79(2):200-11. doi: 10.1016/j.eururo.2020.10.029 Go to original source... Go to PubMed...
    71. de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2020;382(22):2091-102. doi: 10.1056/NEJMoa1911440 Go to original source... Go to PubMed...
    72. Lotan TL, Kaur HB, Salles DC, Murali S, Schaeffer EM, Lanchbury JS, Isaacs WB, Brown R, Richardson AL, Cussenot O, Cancel-Tassin G, Timms KM, Antonarakis ES. Homologous recombination deficiency (HRD) score in germline BRCA2- versus ATM-altered prostate cancer. Mod Pathol 2021;34(6):1185-93. doi: 10.1038/s41379-020-00731-4 Go to original source... Go to PubMed...
    73. Rafiei S, Fitzpatrick K, Liu D, Cai MY, Elmarakeby HA, Park J, Ricker C, Kochupurakkal BS, Choudhury AD, Hahn WC, Balk SP, Hwang JH, Van Allen EM, Mouw KW. ATM Loss Confers Greater Sensitivity to ATR Inhibition Than PARP Inhibition in Prostate Cancer. Cancer Res 2020;80(11):2094-100. doi: 10.1158/0008-5472.CAN-19-3126 Go to original source... Go to PubMed...
    74. Giri VN, Knudsen KE, Kelly WK, Cheng HH, Cooney KA, Cookson MS, Dahut W, Weissman S, Soule HR, Petrylak DP, Dicker AP, AlDubayan SH, Toland AE, Pritchard CC, Pettaway CA, Daly MB, Mohler JL, Parsons JK, Carroll PR, Pilarski R, Blanco A, Woodson A, Rahm A, Taplin ME, Polascik TJ, Helfand BT, Hyatt C, Morgans AK, Feng F, Mullane M, Powers J, Concepcion R, Lin DW, Wender R, Mark JR, Costello A, Burnett AL, Sartor O, Isaacs WB, Xu J, Weitzel J, Andriole GL, Beltran H, Briganti A, Byrne L, Calvaresi A, Chandrasekar T, Chen DYT, Den RB, Dobi A, Crawford ED, Eastham J, Eggener S, Freedman ML, Garnick M, Gomella PT, Handley N, Hurwitz MD, Izes J, Karnes RJ, Lallas C, Languino L, Loeb S, Lopez AM, Loughlin KR, Lu-Yao G, Malkowicz SB, Mann M, Mille P, Miner MM, Morgan T, Moreno J, Mucci L, Myers RE, Nielsen SM, O'Neil B, Pinover W, Pinto P, Poage W, Raj GV, Rebbeck TR, Ryan C, Sandler H, Schiewer M, Scott EMD, Szymaniak B, Tester W, Trabulsi EJ, Vapiwala N, Yu EY, Zeigler-Johnson C, Gomella LG. Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019. J Clin Oncol 2020;38(24):2798-811. doi: 10.1200/JCO.20.00046 Go to original source... Go to PubMed...
    75. Dong H, Hu J, Wang L, Qi M, Lu N, Tan X, Yang M, Bai X, Zhan X, Han B. SOX4 is activated by C-MYC in prostate cancer. Med Oncol 2019;36(11):92. doi: 10.1007/s12032-019-1317-6 Go to original source... Go to PubMed...
    76. Faskhoudi MA, Molaei P, Sadrkhanloo M, Orouei S, Hashemi M, Bokaie S, Rashidi M, Entezari M, Zarrabi A, Hushmandi K, Mirzaei S, Gholami MH. Molecular landscape of c-Myc signaling in prostate cancer: A roadmap to clinical translation. Pathol Res Pract 2022;233:153851. doi: 10.1016/j.prp.2022.153851 Go to original source... Go to PubMed...
    77. Labbé DP, Zadra G, Yang M, Reyes JM, Lin CY, Cacciatore S, Ebot EM, Creech AL, Giunchi F, Fiorentino M, Elfandy H, Syamala S, Karoly ED, Alshalalfa M, Erho N, Ross A, Schaeffer EM, Gibb EA, Takhar M, Den RB, Lehrer J, Karnes RJ, Freedland SJ, Davicioni E, Spratt DE, Ellis L, Jaffe JD, D'Amico AV, Kantoff PW, Bradner JE, Mucci LA, Chavarro JE, Loda M, Brown M. High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program. Nat Commun 2019;10(1):4358. doi: 10.1038/s41467-019-12298-z Go to original source... Go to PubMed...
    78. Fu M, Wang C, Li Z, Sakamaki T, Pestell RG. Minireview: Cyclin D1: normal and abnormal functions. Endocrinology 2004;145(12):5439-47. doi: 10.1210/en.2004-0959 Go to original source... Go to PubMed...
    79. Nakamura Y, Felizola SJ, Kurotaki Y, Fujishima F, McNamara KM, Suzuki T, Arai Y, Sasano H. Cyclin D1 (CCND1) expression is involved in estrogen receptor beta (ERβ) in human prostate cancer. Prostate 2013;73(6):590-5. doi: 10.1002/pros.22599 Go to original source... Go to PubMed...

    This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.


    Return