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Prognostic Significance of PD-L1 and PTEN Expression in Prostatic Cancer

Document Type : Original Article(s)

Authors

1 Department of Pathology, School of Medicine, Zagazig University, Zagazig, Egypt

2 Department of Clinical Oncology and Nuclear Medicine, School of Medicine, Zagazig University, Zagazig, Egypt

Abstract

Background: Programmed death- ligand 1(PD-L1) acts as an immune checkpoint inhibitor. Phosphatase and tensin homolog (PTEN) is a somatically mutated tumor suppressor gene in numerous types of human cancer. The current study aimed to assess the prognostic value of PD-L1 and PTEN expression in prostatic cancer patients, as well as their relationship with the clinicopathological features of the disease.
Method: A total of 55 needle biopsy specimens were retrospectively diagnosed as prostatic adenocarcinoma. Immunohistochemical staining with PD-L1 and PTEN were evaluated in all the cases. The patients were followed up for 5 years in order to detect disease recurrence and survival.
Results: PD-L1 expression in Prostate cancer was positively correlated with high prostatic specific antigen (PSA), higher Gleason score, advanced stage, higher tumor relapse, and worse disease-free and overall survival (P < 0.001). PTEN loss was significantly associated with high PSA, higher Gleason score < 7, advanced tumor stage, tumor relapse, and worse disease-free and overall survival (P < 0.001). We observed a significant negative correlation between PTEN and PD-L1.
Conclusion: PDL-1 and PTEN are prognostic markers for prostate cancer, which can differentiate between the patients who are at a high risk of disease progression and may successively provide novel targeted therapies.

Keywords

Full Text

How to cite this article:

Elaidy NF, Abdelbary EH, Hegazy MW, Elwan A. Prognostic significance of PD-L1 and PTEN expression in prostatic cancer. Middle East J Cancer. 2 0 2 2 ; 1 3 ( 2 ) : 2 4 7 - 5 4 . doi:10.30476/mejc.2021.87068. 1393.

References
  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34. doi: 10.3322/caac.21551.
  2. Ibrahim AS, Khaled HM, Mikhail NN, Baraka H, Kamel H. Cancer incidence in Egypt: results of the national population-based cancer registry program. J Cancer Epidemiol. 2014;2014:437971. doi:10.1155/2014/437971.
  3. Van den Broeck T, van den Bergh RCN, Arfi N, Gross T, Moris L, Briers E, et al. Prognostic value of biochemical recurrence following treatment with curative intent for prostate cancer: A systematic review. Eur Urol. 2019;75(6):967-87. doi: 10.1016/j.eururo.2018.10.011.
  4. Chen J, Jiang CC, Jin L, Zhang XD. Regulation of PD-L1: a novel role of pro-survival signalling in cancer. Ann Oncol. 2016;27(3):409-16. doi: 10.1093/annonc/mdv615.
  5. Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018; 359(6382):1350-55.doi: 10.1126/science.aar4060.
  6. Zhang Y, Kang S, Shen J, He J, Jiang L, Wang W, et al. Prognostic significance of programmed cell death 1 (PD-1) or PD-1 ligand 1 (PD-L1) expression in epithelial-originated cancer:a meta-analysis. Medicine (Baltimore). 2015;94(6):e515.doi: 10.1097/MD.0000000000000515.
  7. Lu X, Horner JW, Paul E, Shang X, Troncoso P, Deng P, et al., Effective combinatorial immunotherapy for castration-resistant prostate cancer. Nature. 2017; 543(7647):728-32. doi: 10.1038/nature21676.
  8. Lee YR, Chen M, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor: new modes and prospects. Nat Rev Mol Cell Biol. 2018 ;19(9):547-62. doi: 10.1038/s41580-018-0015-0.
  9. Wise HM, Hermida MA, Leslie NR. Prostate cancer, PI3K, PTEN and prognosis. Clin Sci. 2017; 131:197-210.doi: 10.1042/CS20160026.
  10. Mithal P, Allott E, Gerber L, Reid J, Welbourn W, Tikishvili E, et al. PTEN loss in biopsy tissue predicts poor clinical outcomes in prostate cancer. Int J Urol. 2014;21(12):1209-14. doi: 10.1111/iju.12571.
  11. Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE. The 2016 WHO classification of tumours of the urinary system and male genital organs-part B: prostate and bladder tumours. Eur Urol. 2016;70(1):106-19. doi: 10.1016/j.eururo.2016.02.028.
  12. Hsu SM, Raine L, Fanger H. Use of Avidin Biotin peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981;29(4):577-80. doi :10.1177 /29.4. 61 66661.
  13. Li H, Wang Z, Zhang Y, Sun G, Ding B, Yan L, et al. The immune checkpoint regulator PDL1 is an independent prognostic biomarker for biochemical recurrence in prostate cancer patients following adjuvant hormonal therapy. J Cancer. 2019;10(14): 3102-11. doi: 10.7150/jca.30384.
  14. Hamid AA, Gray KP, Huang Y, Bowden M, Pomerantz M, Loda M, et al. Loss of PTEN expression detected by fluorescence immunohistochemistry predicts lethal prostate cancer in men treated with prostatectomy. Eur Urol Oncol. 2019;2(5):475-82. doi:
    1016/j.euo.2018.09.003.
  15. Gevensleben H, Dietrich D, Golletz C, Steiner S, Jung M, Thiesler T, et al. The immune checkpoint regulator PD-l1 is highly expressed in aggressive primary prostate cancer. Clin Cancer Res. 2016;22(8):1969-77. doi: 10.1158/1078-0432.CCR-15-2042.
  16. Massari F, Ciccarese C, Caliò A, Munari E, Cima L, Porcaro AB, et al. Magnitude of PD-1, PD-L1 and T lymphocyte expression on tissue from castrationresistant prostate adenocarcinoma: An exploratory analysis. Target Oncol. 2016;11(3):345-51. doi: 10.1007/s11523-015-0396-3.
  17. Xian P, Ge D, Wu VJ, Patel A, Tang WW, Wu X, et al. PD-L1 instead of PD-1 status is associated with the clinical features in human primary prostate tumors. Am J Clin Exp Urol. 2019;15;7(3):159-69.
  18. Haffner MC, Guner G, Taheri D, Netto GJ, Palsgrove DN, Zheng Q, et al. Comprehensive evaluation of programmed death-ligand 1 expression in primary and metastatic prostate cancer. Am J Pathol. 2018;188(6):1478-85. doi:10.1016/j.ajpath.2018.02.014.
  19. Sharma M, Yang Z, Miyamoto H. Immunohistochemistry of immune checkpoint markers PD-1 and PD-L1 in prostate cancer. Medicine (Baltimore). 2019;98(38):e17257. doi: 10.1097/MD.0000000000017257.
  20. Ness N, Andersen S, Khanehkenari MR, Nordbakken CV, Valkov A, Paulsen EE, et al. The prognostic role of immune checkpoint markers programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PDL1) in a large, multicenter prostate cancer cohort. Oncotarget. 2017;8(16):26789-801.doi: 10.18632/oncotarget.15817.
  21. Petitprez F, Fossati N, Vano Y, Freschi M, Becht E, Lucianò R, et al. PD-L1 expression and CD8+ T-cell infiltrate are associated with clinical progression in patients with node-positive prostate cancer. Eur Urol Focus. 2019;5(2):192-6. doi: 10.1016/j.euf.2017.05.013.
  22. Noh BJ, Sung JY, Kim YW, Chang SG, Park YK. Prognostic value of ERG, PTEN, CRISP3 and SPINK1 in predicting biochemical recurrence in prostate cancer. Oncol Lett. 2016;11(6):3621-30. doi: 10.3892/ol.2016.4459.
  23. Lotan TL, Heumann A, Rico SD, Hicks J, Lecksell K, Koop C, et al. PTEN loss detection in prostate cancer: comparison of PTEN immunohistochemistry and PTEN FISH in a large retrospective prostatectomy cohort. Oncotarget. 2017;8(39):65566-76. doi:10.18632/oncotarget.19217.
  24. Cuzick J, Yang ZH, Fisher G, Tikishvili E, Stone S, Lanchbury JS, et al. Prognostic value of PTEN loss in men with conservatively managed localised prostate cancer. Br J Cancer. 2013;108(12):2582-9. doi:10.1038/bjc.2013.248.
  25. Guedes LB, Tosoian JJ, Hicks J, Ross AE, Lotan TL. PTEN loss in gleason score 3 + 4 = 7 prostate biopsies is associated with nonorgan confined disease at radical prostatectomy. J Urol. 2017;197(4):1054-9. doi: 10.1016/j.juro.2016.09.084.
  26. Mehra R, Salami SS, Lonigro R, Bhalla R, Siddiqui J, Cao X, et al. Association of ERG/PTEN status with biochemical recurrence after radical prostatectomy for clinically localized prostate cancer. Med Oncol. 2018;35(12):152. doi: 10.1007/s12032-018-1212-6.
  27. Léon P, Cancel-Tassin G, Drouin S, Audouin M, Varinot J, Comperat E, et al. Comparison of cell cycle progression score with two immunohistochemical markers (PTEN and Ki-67)for predicting outcome in prostate cancer after radical prostatectomy. World J Urol. 2018;36(9):1495-500. doi: 10.1007/s00345-018-2290-y.
  28. Lokman U, Erickson AM, Vasarainen H, Rannikko AS, Mirtti T. PTEN loss but not ERG expression in diagnostic biopsies is associated with increased risk of progression and adverse surgical findings in men with prostate cancer on active surveillance. Eur Urol Focus. 2018;4(6):867-73. doi: 10.1016/j.euf.2017.03.004.
  29. Giannico GA, Arnold SA, Gellert LL, Hameed O. New and emerging diagnostic and prognostic immunohistochemical biomarkers in prostate pathology. Adv Anat Pathol. 2017;24(1):35-44. doi: 10.1097/PAP.0000000000000136.
  30. Peng W, Chen JQ, Liu C, Malu S, Creasy C, Tetzlaff MT, et al. Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov. 2016;6(2):202-16. doi: 10.1158/2159-8290.CD-15-0283.
  31. Vidotto T, Saggioro FP, Jamaspishvili T, Chesca DL, Picanço de Albuquerque CG, Reis RB, et al. PTENdeficient prostate cancer is associated with an immunosuppressive tumor microenvironment mediated by increased expression of IDO1 and infiltrating FoxP3+ T regulatory cells. Prostate. 2019;79(9):969-79. doi: 10.1002/pros.23808.
  32. Jamaspishvili T, Berman DM, Ross AE, Scher HI, De Marzo AM, Squire JA, et al. Clinical implications of PTEN loss in prostate cancer. Nat Rev Urol. 2018;15(4):222-34. doi: 10.1038/nrurol.2018.9.
Middle East Journal of Cancer
Volume 13, Issue 2 - Serial Number 50
April 2022
Pages 247-254
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