Document Type : Original Article

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

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.

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.000000
0000000515.
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:
10.1016/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.000000
0000017257.
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.