Prognostic significance of tumor suppressor protein p53 in prostate cancer

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Published Feb 18, 2024
https://doi.org/10.62438/tunismed.v102i2.4730
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Vol. 102 No. 2 (2024): Tunis med feb 2024

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Sarra Ben Rejeb
Department of pathology, Internal security forces hospital, Tunis, Tunisia
Nadia Kouki
Department of pathology, Internal security forces hospital, Tunis, Tunisia
Sirine Elfekih
Department of pathology, Internal security forces hospital, Tunis, Tunisia
Ines Cherif
Department of pathology, Internal security forces hospital, Tunis, Tunisia
Hassen Khouni
Department of urology, Internal security forces hospital, Tunis, Tunisia

Abstract

Backround: The p53 gene mutation is one of the most common genetic alterations in many cancers. In prostate cancer (PCa), it has been associated with a poor prognosis, tumor progression and aggressiveness. P53 mutation induces an abnormal protein expression in related tissues.


Aim: This study aimed to assess p53 expression using immunohistochemistry in PCa and to discuss its prognostic value.


Methods: We have retrospectively collected all cases of PCa diagnosed in our pathology department between 2012 and 2022. An automatized immunohistochemical analysis was performed using monoclonal p53 antibody. For each case, we assessed the proportion of positive cells and the intensity of staining. P53 expression was considered abnormal when it was totally negative or overexpressed (>=50% of positive cells).


Results: Twenty-four cases have been selected. Abnormal p53 expression was found in 42% of cases (P53 was overexpressed in 6cases and totally negative in 4 cases). Mean age of patients with p53 abnormal expression was 70years old. Patients with p53 abnormal expression had Gleason score >7 in 5 cases, ISUP grade >2 in 3 cases, peri-neural invasion in 8cases, capsule invasion in 9cases. All patients with p53 overexpression developed androgen resistance (p<0.01).


Conclusion: An aberrant expression profile of the p53 protein was observed in 42% of cases, and a statistically significant association was found with androgen resistance. Our results suggest a potential prognostic role of p53 in PCa.

Keywords:

prostate carcinoma, p53, immunohistochemistry

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References

  1. Rawla P. Epidemiology of Prostate Cancer. World J Oncol. 2019;10:63–89.
  2. Ehsani M, David FO, Baniahmad A. Androgen Receptor-Dependent Mechanisms Mediating Drug Resistance in Prostate Cancer. Cancers. 2021;13:1534.
  3. Maughan BL, Antonarakis ES. Androgen pathway resistance in prostate cancer and therapeutic implications. Expert Opinion on Pharmacotherapy. 2015;16:1521–1537.
  4. Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013;500:415–421.
  5. Sivoňová MK, Vilčková M, Kliment J, et al. Association of p53 and p21 polymorphisms with prostate cancer. Biomedical Reports. 2015;3:707–714.
  6. Foster CS, McLoughlin J, Bashir I, et al. Markers of the metastatic phenotype in prostate cancer. Hum Pathol. 1992;23:381–394.
  7. Cappello F, Rappa F, David S, et al. Immunohistochemical evaluation of PCNA, p53, HSP60, HSP10 and MUC-2 presence and expression in prostate carcinogenesis. Anticancer Res. 2003;23:1325–1331.
  8. Barbieri CE, Baca SC, Lawrence MS, et al. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat Genet. 2012;44:685–689.
  9. Bookstein R, MacGrogan D, Hilsenbeck SG, et al. p53 is mutated in a subset of advanced-stage prostate cancers. Cancer Res. 1993;53:3369–3373.
  10. Hall MC, Navone NM, Troncoso P, et al. Frequency and characterization of p53 mutations in clinically localized prostate cancer. Urology. 1995;45:470–475.
  11. Heidenberg HB, Sesterhenn IA, Gaddipati JP, et al. Alteration of the tumor suppressor gene p53 in a high fraction of hormone refractory prostate cancer. J Urol. 1995;154:414–421.
  12. Beltran H, Yelensky R, Frampton GM, et al. Targeted next-generation sequencing of advanced prostate cancer identifies potential therapeutic targets and disease heterogeneity. Eur Urol. 2013;63:920–926.
  13. Hamid AA, Gray KP, Shaw G, et al. Compound Genomic Alterations of TP53, PTEN, and RB1 Tumor Suppressors in Localized and Metastatic Prostate Cancer. Eur Urol. 2019;76:89–97.
  14. van Dessel LF, van Riet J, Smits M, et al. The genomic landscape of metastatic castration-resistant prostate cancers reveals multiple distinct genotypes with potential clinical impact. Nat Commun. 2019;10:5251.
  15. Cancer Genome Atlas Research Network. The Molecular Taxonomy of Primary Prostate Cancer. Cell. 2015;163:1011–1025.
  16. Nientiedt C, Budczies J, Endris V, et al. Mutations in TP53 or DNA damage repair genes define poor prognostic subgroups in primary prostate cancer. Urologic Oncology: Seminars and Original Investigations. 2022;40:8.e11-8.e18.
  17. Mateo J, Seed G, Bertan C, et al. Genomics of lethal prostate cancer at diagnosis and castration resistance. J Clin Invest. 2020;130:1743–1751.
  18. Hong MKH, Macintyre G, Wedge DC, et al. Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer. Nat Commun. 2015;6:6605.
  19. Nientiedt C, Endris V, Jenzer M, et al. High prevalence of DNA damage repair gene defects and TP53 alterations in men with treatment-naïve metastatic prostate cancer -Results from a prospective pilot study using a 37 gene panel. Urol Oncol. 2020;38:637.e17-637.e27.
  20. Gesztes W, Lap C, Dalivand M, et al. Evaluating p53 nuclear expression and prostate cancer progression in a predominantly African American cohort. JCO. 2023;41:217–217.
  21. Schlomm T, Iwers L, Kirstein P, et al. Clinical significance of p53 alterations in surgically treated prostate cancers. Mod Pathol. 2008;21:1371–1378.
  22. Deliveliotis C, Skolarikos A, Karayannis A, et al. The prognostic value of p53 and DNA ploidy following radical prostatectomy. World J Urol. 2003;21:171–176.
  23. Gesztes W, Schafer C, Young D, et al. Focal p53 protein expression and lymphovascular invasion in primary prostate tumors predict metastatic progression. Sci Rep. 2022;12:5404.
  24. Petrescu A, Mârzan L, Codreanu O, et al. Immunohistochemical detection of p53 protein as a prognostic indicator in prostate carcinoma. Rom J Morphol Embryol. 2006;47:143–146.
  25. Guedes LB, Almutairi F, Haffner MC, et al. Analytic, Preanalytic, and Clinical Validation of p53 IHC for Detection of TP53 Missense Mutation in Prostate Cancer. Clin Cancer Res. 2017;23:4693–4703.
  26. Visakorpi T, Kallioniemi OP, Heikkinen A, et al. Small subgroup of aggressive, highly proliferative prostatic carcinomas defined by p53 accumulation. J Natl Cancer Inst. 1992;84:883–887.
  27. Maughan BL, Guedes LB, Boucher K, et al. p53 status in the primary tumor predicts efficacy of subsequent abiraterone and enzalutamide in castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2018;21:260–268.
  28. Robinson D, Van Allen EM, Wu Y-M, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015;161:1215–1228.
  29. Westaby D, Viscuse PV, Ravilla R, et al. Beyond the Androgen Receptor: The Sequence, the Mutants, and New Avengers in the Treatment of Castrate-Resistant Metastatic Prostate Cancer. American Society of Clinical Oncology Educational Book. 2021;e190–e202.
  30. Hientz K, Mohr A, Bhakta-Guha D, et al. The role of p53 in cancer drug resistance and targeted chemotherapy. Oncotarget. 2017;8:8921–8946.
  31. Bykov VJN, Wiman KG. Mutant p53 reactivation by small molecules makes its way to the clinic. FEBS Lett. 2014;588:2622–2627.