Assessment of Immunohistochemical Expression of Programmed Cell Death Ligand-1 in Invasive Urothelial Carcinoma
DOI:
https://doi.org/10.21276/apalm.3398Keywords:
Immunohistochemistry, PDL-1, Invasive urothelial carcinoma, Urinary bladder, HematuriaAbstract
Background: Infiltrating urothelial carcinoma is the most common histological variant (23.1%). This study was conducted to evaluate the immunohistochemical expression of PD-L1 in invasive urothelial carcinoma and to correlate PD-L1 expression with demographic data and the histological grade of urothelial carcinoma.
Methods: The study comprised a total of 65 cases of muscle-invasive urothelial carcinoma collected over a period of one year and evaluated for PD-L1 expression using the immunohistochemistry technique.
Results: Infiltrating urothelial carcinoma was the most common histological variant (23.1%), followed by poorly differentiated carcinoma (16.9%). PD-L1 positivity was observed in 47.7% of the total cases, while the remaining 52.3% showed no expression of PD-L1. Among the various histologic variants, poorly differentiated carcinoma (57.1%) was the largest group with weak expression of PD-L1; infiltrating urothelial carcinoma (26.7%) was the largest group with moderate expression of PD-L1, while the lymphoepithelioma-like variant (66.7%) was the largest group with strong expression of PD-L1. Our study was in concordance with other studies, showing that PD-L1 expression is not associated with clinicopathologic features like age, gender, and smoking status.
Conclusion: The present study shows a significant difference between the various groups in terms of the distribution of histologic variants and PD-L1 positivity according to the WHO classification (2016) as well as severity scoring by the IHC technique.
References
1. Ghervan L, Zaharie A, Ene B, Elec F. Small cell carcinoma of urinary bladder: where do we stand? Clujul Med. 2017;90:13-7.
2. Wallerand H, Bernhard J, Culive S, Ballanger P, Robert G, Reiter RE, et al. Targeted therapies in non-muscle-invasive bladder cancer according to the signalling pathways. Urol Oncol. 2011;29(1):4-11.
3. Saginala K, Barsouk A, Aluru JS, Rawla P, Padala SA, Barsoul A. Epidemiology of bladder cancer - review. Med Sci. 2020;8(1):15.
4. Talaska G. Aromatic amines and human urinary bladder cancer: exposure sources and epidemiology. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2003;21:29-43.
5. Baris D, Waddell R, Bcane, Schwenn M, Colt J, Ayotte J, et al. Elevated bladder cancer in northern New England: the role of drinking water and arsenic. J Natl Cancer Inst. 2016;1018:1-9.
6. Sun JW, Zhao LG, Yang Y, Ma X, Wang YY, Xiang YB. Obesity and risk of bladder cancer: a dose-response meta-analysis of 15 cohort studies. PLoS One. 2015;10(3)
7. Yu C, Hegun C, Longfei L, Long W, Zhi C, Feng Z, et al. GSTM1 and GSTT1 polymorphisms are associated with increased bladder cancer risk: Evidence from updated meta-analysis. Oncotarget. 2017;8:3246-58.
8. Horstmann M, Witthohn R, Falk M, Stenzl A. Gender-specific differences in bladder cancer: a retrospective analysis. Gend Med. 2018;5(4):385-94.
9. Netto GJ, Amin MB. The lower urinary tract and male genital system. In: Kumar V, Abbas AK, Aster JC, Turner JR, editors. Robbins and Cotran Pathologic Basis of Disease. Vol. 2. 10th ed. South Asia ed. Chicago: Elsevier; 2020. p. 955-62.
10. Filipovic A, Miller J, Bolen J. Progress toward identifying exact proxies for predicting response to immunotherapies. Front Cell Dev Biol. 2020;8:155.
11. Kythreotou A, Siddique A, Mauri FA, Bower M, Pinato DJ. PD-L1. J Clin Pathol. 2018;71(3):189-94.
12. Tojyo I, Shintani Y, Nakanishi T, Okamoto K, Hiraishi Y, Fujita S, et al. PD-L1 expression correlated with p53 expression in oral squamous cell carcinoma. Maxillofac Plast Reconstr Surg. 2019;41:56.
13. Bellmunt J, Mullane S, Werner L, Fay A, Callea M, Leow J, et al. Association of PD-L1 expression on tumor-infiltrating mononuclear cells and overall survival in patients with urothelial carcinoma. Ann Oncol. 2015;26:4.
14. Feng M, Xu L, He Y, Sun L, Zhang Y, Wang W. Clinical significance of PD-L1 enhanced expression in cervical squamous cell carcinoma. Int J Clin Exp Pathol. 2018;11(11):5370-8.
15. Jackson P, Blythe D. Immunohistochemical techniques. In: Bancroft JD, Gamble M, editors. Theory and practice of histochemical technique. 7th ed. New York: Churchill Livingstone; 2012. p. 381-426.
16. Biomedical Waste Management (Amendment) Rules 2018. New Delhi: Gazette of India, Extraordinary, Part II, Section 3, Subsection (i); 2018 Mar 16.
17. Wang L, Sfakianos JP, Beaumont KG, Akturk G, Horowitz, Sebra RP, et al. Myeloid cell-associated resistance to PD-1/PD-L1 blockade in urothelial cancer revealed through bulk and single-cell RNA sequencing. Clin Cancer Res. 2021;27(15):4287-300.
18. Jung I, Messing E. Molecular mechanisms and pathways in bladder cancer development and progression. Cancer Control. 2000;7(4):325-34.
19. Jones TD, Wang M, Eble JN, Maclennan GT, Beltran A, Zhang S, et al. Molecular evidence supporting field effect in urothelial carcinogenesis. Clin Cancer Res. 2005;11(18):6512-9.
20. Goux CL, Damotte D, Vacher S, Sibony M, Delong NB, Schnitzler A, et al. Correlation between mRNA expression and protein expression of immune checkpoint-associated molecules in bladder urothelial cancer: a retrospective study. Urol Oncol. 2017;35(5):257-63.
21. Stella J, Bavaresco L, Braganhol E, Rockenbach L, Parias PF. Differential ectonucleotidase expression in human bladder cancer cell lines. Urol Oncol. 2010;28(3):260-7.
22. Hashmi AA, Rafique S, Haider R, Munawar S, Irfan M, Ali J. Prognostic implications of deep muscle invasion and high grade for bladder urothelial carcinoma. Cureus. 2020;12(10)
23. Gajjar D, Faujdar M, Jain R, Gupta S. Histomorphological spectrum of urothelial tumors according to WHO/ISUP consensus classification (2016): tertiary care center study. Int J Clin Diagn Pathol. 2019;2(1):191-5.
24. Xylinas E, Robinson BD, Kluth LA, Volkmer BG, Hautmann R, Kufer R, et al. Association of T cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of bladder. Eur J Surg Oncol. 2014;40(1):121-7.
25. Davis AA, Patel VG. The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors. J Immunother Cancer. 2019;7:278.
26. Gandini S, Massi D, Mandala M. PDL1 expression in cancer patients receiving anti PD1/PDL1 antibodies: a systematic review and meta-analysis. Crit Rev Oncol Hematol. 2016;100:88-98.
27. Owyong M, Lotan Y, Kapur P, Panwar V, McKenzie T, Lee TK, et al. Expression and prognostic utility of PD-L1 in patients with squamous cell carcinoma of the bladder. Urol Oncol. 2019;37(7):478-84.
28. Wu CT, Chen WC, Chang YH, Lin W, Chen MF. The role of PD-L1 in the radiation response and clinical outcome for bladder cancer. Sci Rep. 2016;6:19740.
29. Li Q, Li F, Che J, Zhao Y, Qiao C. Expression of B7 Homolog 1 (B7H1) is associated with clinicopathologic features in urothelial bladder cancer. Med Sci Monit. 2018;24:7303-8.
30. Takahara T, Murase Y, Tsuzuki T. Urothelial carcinoma: variant histology, molecular subtyping, and immunophenotyping significant for treatment outcomes. Pathology. 2021;53(1):56-66.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Aakanksha Rawat, Monika Gupta, Devendra Singh Pawar, Sunita Singh, Sujata Kumari
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access at http://opcit.eprints.org/oacitation-biblio.html).