Expression of PD-L1, AR, and P53 in urothelial carcinoma and their correlation with clinical prognosis

doi:10.16150/j.1671-2870.2025.03.007

Abstract

Abstract:

Objective This study aims to observe the expression of programmed cell death 1 ligand 1 (PD-L1), P53, and androgen receptor (AR) in tumor tissues of patients with urothelial carcinoma (UC) and analyze their correlation with patient prognosis. Methods A retrospective analysis was conducted on 115 UC patients with complete clinical data who were admitted consecutively to the General Hospital of Eastern Theater Command and Nanjing Drum Tower Hospital from May 2017 to February 2020. Immunohistochemistry was used to detect the expression of PD-L1, P53, and AR proteins in pathological tissues. The chi-square test (χ² test) was employed to analyze the correlation between these biomarkers and clinicopathological characteristics. Kaplan-Meier survival analysis was used to evaluate the relationship between biomarker expression and prognosis. Results The median follow-up time for the study cohort was 32.5 months (range: 1-54 months). Disease progression occurred in 22 cases, and 17 patients (17.2%) died. The expression rates of PD-L1, P53, and AR in UC tissues were 46.1%, 45.2%, and 7.8%, respectively. Positive PD-L1 expression was associated with clinical progression (54.9% in the positive group vs. 31.8% in the negative group, P=0.016). AR-positive cases were more likely to exhibit multifocal tumor growth (21.7% vs. 4.3%, P=0.019). P53 expression showed no significant correlation with the clinical characteristics of UC. The positive expression of PD-L1, P53, and AR was not associated with overall survival in UC patients. Conclusion Positive PD-L1 expression is associated with disease progression in UC. The expression of PD-L1, P53, and AR is not correlated with short-term survival prognosis in UC patients. Among them, AR expression rate is low and shows no association with short-term prognosis, suggesting that AR-targeted therapy for UC patients has certain limitations.

Key words: Urothelial carcinoma, Clinicopathology, Programmed cell death 1 ligand 1, Androgen receptor, Prognosis

CLC Number:

R737.15
R449

ZHOU Xiaodie, Qi Rongxin, WANG Xuan, YU Bo, WANG Jianjun, SHI Qunli, RAO Qiu, BAO Wei. Expression of PD-L1, AR, and P53 in urothelial carcinoma and their correlation with clinical prognosis[J]. Journal of Diagnostics Concepts & Practice, 2025, 24(03): 286-292.

Figures/Tables 4

Table 1

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References 20

[1]	ECKSTEIN M, CIMADAMORE A, HARTMANN A, et al. PD-L1 assessment in urothelial carcinoma: a practical approach[J]. Ann Transl Med, 2019, 7(22):690. doi: 10.21037/atm.2019.10.24 pmid: 31930091
[2]	国家病理质控中心, 中华医学会病理学分会, 中国临床肿瘤学会肿瘤病理专家委员会. 实体肿瘤PD-L1免疫组织化学检测专家共识(2021版)[J]. 中华病理学杂志, 2021, 50(7):710-718.
	Pathology Quality Control Center, Chinese Society of Pathology, Pathology Committee of Chinese Society of Clinical Oncology. Consensus on the immunohistochemical tests of PD-L1 in solid tumors (2021 version)[J]. Chin J Pathol, 2021, 50(7):710-718.
[3]	HODGSON A, XU B, DOWNES M R. p53 immunohistochemistry in high-grade urothelial carcinoma of the bladder is prognostically significant[J]. Histopathology, 2017, 71(2):296-304. doi: 10.1111/his.13225 pmid: 28342221
[4]	RAMMAL R, GOEL K, ELISHAEV E, et al. The utility of SOX10 immunohistochemical staining in breast patho-logy[J]. Am J Clin Pathol, 2022, 158(5):616-625.
[5]	ROSE T L, MILOWSKY M I. Checkpoint inhibition: a new beginning for urothelial cancer[J]. Lancet Oncol, 2017, 18(2):160-161. doi: S1470-2045(16)30675-1 pmid: 28081913
[6]	BALAR A V, CASTELLANO D, O'DONNELL P H, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study[J]. Lancet Oncol, 2017, 18(11):1483-1492. doi: S1470-2045(17)30616-2 pmid: 28967485
[7]	MUNARI E, QUERZOLI G, BRUNELLI M, et al. Comparison of three validated PD-L1 immunohistochemical assays in urothelial carcinoma of the bladder: interchangeability and issues related to patient selection[J]. Front Immunol, 2022,13:954910.
[8]	LIU J, ZHANG C, HU J, et al. Effectiveness of anti-PD-1/PD-L1 antibodies in urothelial carcinoma patients with different PD-L1 expression levels: a meta-analysis[J]. Oncotarget, 2018, 9(15):12400-12407. doi: 10.18632/oncotarget.24249 pmid: 29552320
[9]	WARD M, ALBERTSON D, FURTADO L V, et al. PD-L1 tumor cell expression in upper tract urothelial carcinomas is associated with higher pathologic stage[J]. Appl Immunohistochem Mol Morphol, 2022, 30(1):56-61.
[10]	ZHONG Q, SHOU J, YING J, et al. High PD-L1 expression on immune cells, but not on tumor cells, is a favora-ble prognostic factor in urothelial carcinoma[J]. Future Oncol, 2021, 17(22):2893-2905.
[11]	RUBINO S, KIM Y, ZHOU J, et al. Positive Ki-67 and PD-L1 expression in post-neoadjuvant chemotherapy muscle-invasive bladder cancer is associated with shorter overall survival: a retrospective study[J]. World J Urol, 2021, 39(5):1539-1547.
[12]	周晓蝶, 陈巍魏, 余波, 等. 尿路上皮癌的临床病理学特征[J]. 诊断学理论与实践, 2023, 22(3):292-299.
	ZHOU X D, CHEN W W, YV B, et al. Clinicopathological features of urothelial carcinoma[J]. J Diagn Concepts Pract, 2023, 22(3):292-299.
[13]	陈荧野, 陈勇, 姜庆, 等. NLR及PLR对晚期尿路上皮癌免疫治疗疗效和预后的预测价值[J]. 重庆医科大学学报, 2023, 48(8):965-970.
	CHE Y Y, CHE Y, JIANG Q, et al. Predictive value of NLR and PLR for outcome after immunotherapy in advanced urothelial carcinoma[J]. J Chongqing Med Univ, 2023, 48(8):965-970.
[14]	KNOWLES M A, HURST C D. Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity[J]. Nat Rev Cancer, 2015, 15(1):25-41. doi: 10.1038/nrc3817 pmid: 25533674
[15]	CHATTERJEE S J, DATAR R, YOUSSEFZADEH D, et al. Combined effects of p53, p21, and pRb expression in the progression of bladder transitional cell carcinoma[J]. J Clin Oncol, 2004, 22(6):1007-1013. pmid: 14981105
[16]	ESRIG D, SPRUCK C H 3RD, NICHOLS P W, et al. p53 nuclear protein accumulation correlates with mutations in the p53 gene, tumor grade, and stage in bladder cancer[J]. Am J Pathol, 1993, 143(5):1389-1397. pmid: 7901994
[17]	THAKUR B, KISHORE S, DUTTA K, et al. Role of p53 and Ki-67 immunomarkers in carcinoma of urinary bladder[J]. Indian J Pathol Microbiol, 2017, 60(4):505-509.
[18]	TRIPATHI A, GUPTA S. Androgen receptor in bladder cancer: A promising therapeutic target[J]. Asian J Urol, 2020, 7(3):284-290. doi: 10.1016/j.ajur.2020.05.011 pmid: 32742928
[19]	ELZAMY S, MS A A, KANDEEL W. The prognostic significance of androgen receptor and β-catenin immunohistochemical expression in urothelial carcinoma with and without detrusor muscle invasion from an Egyptian institution[J]. Pol J Pathol, 2018, 69(3):234-242.
[20]	NAM J K, PARK S W, LEE S D, et al. Prognostic value of sex-hormone receptor expression in non-muscle-invasive bladder cancer[J]. Yonsei Med J, 2014, 55(5):1214-1221. doi: 10.3349/ymj.2014.55.5.1214 pmid: 25048477

Patient charateristics	PD-L1	P53	AR	Ki-67（≥30%）
Positive cases	53（46.1）	52（45.2）	9（7.8）	63（54.8）
Gender
Male	45（46.4）	48（44.4）	7（7.2）	53（54.6）
Female	8（44.4）	4（45.4）	2（11.1）	10（55.6）
Neural invasion
No	36（41.9）	36（41.9）	6（7.0）	47（54.7）
Yes	17（58.6）	16（55.2）	3（10.3）	16（55.2）
Vascular invasion
No	30（41.7）	31（43.1）	4（5.6）	33（45.8）
Yes	23（53.5）	21（48.8）	5（11.6）	30（69.8）^*
AJCC clinical staging
Ⅰ/Ⅱ	14（31.8）	15（34.1）	3（6.8）	20（45.5）
Ⅲ/Ⅳ	39（54.9）^＊	37（52.1）	6（8.5）	43（60.6）
Primary site
UB	66（82.5）	39（48.8）	8（10.0）	29（36.3）
Upper tract	30（85.7）	18（51.4）	1（0.9）	13（37.1）
Single/multifocal
Single	43（46.7）	41（44.6）	4（4.3）	48（52.2）
Multifocal	10（43.5）	11（47.8）	5（21.7）^＊	15（65.2）
With carcinoma in situ
Without	44（46.3）	42（44.2）	5（5.3）	50（52.6）
With	9（45.0）	10（50.0）	4（20.0）	13（65.0）
UC subtype, n(%)
Low-grade	1（20.0）	2（40.0）	0（0.0）	0（0.0）
High-grade	33（48.5）	26（38.2）	5（7.4）	36（52.9）
Histological type	19（45.2）	24（57.1）	4（9.5）	27（64.3）
Lymph node metastasis
No	25（41.0）	36（41.0）	3（4.9）	35（57.4）
Yes	17（63.0）	16（59.3）	2（7.4）	19（70.4）