Document Type : Research Paper

Authors

Department of Pathology, College of Medicine, University of Mosul, Mosul, Iraq

Abstract

Background and objectives: To evade anti-tumour responses, tumour cells expressed programmed death ligand 1 (PDL1), which play a role in suppressing the adaptive arm of immune systems. It has been disputed, meanwhile, whether PDL1 expression in Renal cell cancer (RCC) has any predictive value. Anti-PDL1 can decrease tumour size, inhibit immunological checkpoints, and improve overall RCC survival. In our study, our primary objective was to evaluate the statement of PDL1 immunostain in RCC. Methods: Fifty samples of primary RCC were used in a prospective and retrospective case series research. From Formalin-fixed and paraffin-embedded (FFPE) blocks, hematoxylin and eosin (H and E) stained glass slides were prepared, and the diagnosis was updated. PDL1 immunohistochemical stain (PDL1 IHC) was conducted for all cases, using the EnVision FLEX visualization system on Autostainer Link 48 with PDL1 IHC 22C3 pharmDx (Dako) monoclonal mouse anti-PDL1. Results: PDL1 is found to be expressed in (56 %). The mean age of patients was (54.8±13.52) years, most of them were in their 50s and 60s year old, with male to female ratio of 1.94:1. Clear cell RCC consists of (78%), and most common in stage 1 and stage 3 with statistically significant p–value. Clear cell carcinoma was statistically significant with stage 1 and 3 and grade 2 was the most frequent. The majority of instances of clear cell RCC were on the left side. Conclusion: PDL1 provide an excellent template for confirming the diagnosis of RCC.

Keywords

Main Subjects

  1. Walter B, Gil S, Naizhen X, Kruhlak MJ, Linehan WM, Srinivasan R, et al. Determination of the expression of PD-L1 in the morphologic spectrum of renal cell carcinoma. Journal of Cancer. 2020;11(12):3596.
  2. Makino T, Kadomoto S, Izumi K, Mizokami A. Epidemiology and prevention of renal cell carcinoma. 2022;14(16):4059.
  3. Bukavina L, Bensalah K, Bray F, Carlo M, Challacombe B, Karam JA, et al. Epidemiology of renal cell carcinoma: 2022 update. European urology. 2022;82(5):529-42.
  4. Howlader N, Noone AM, Krapcho ME, Miller D, Bishop K, Altekruse SF, et al. SEER cancer statistics review, 1975-2013, national cancer institute. bethesda, MD.
  5. Moch H, Amin MB, Berney DM, Compérat EM, Gill AJ, Hartmann A, et al. The 2022 World Health Organization classification of tumours of the urinary system and male genital organs—part A: renal, penile, and testicular tumours. European urology. 2022 Jul 16.
  6. Sanmamed MF, Chen L. Inducible expression of B7-H1 (PD-L1) and its selective role in tumor site immune modulation. Cancer journal. 2014 Jul;20(4):256.
  7. Sharpe AH, Wherry EJ, Ahmed R, Freeman GJ. The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nature immunology. 2007;8(3):239-45.
  8. Ohaegbulam KC, Assal A, Lazar-Molnar E, Yao Y, Zang X. Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends in molecular medicine. 2015;21(1):24-33.
  9. Carlsson J, Sundqvist P, Kosuta V, Fält A, Giunchi F, Fiorentino M, et al. PD-L1 expression is associated with poor prognosis in renal cell carcinoma. Applied Immunohistochemistry and Molecular Morphology. 2020;28(3):213-20.
  10. Ueda K, Suekane S, Kurose H, Chikui K, Nakiri M, Nishihara K, et al. Prognostic value of PD-1 and PD-L1 expression in patients with metastatic clear cell renal cell carcinoma. InUrologic Oncology: Seminars and Original Investigations 2018;Vol. 36(11):499-e9.
  11. Escudier B, Porta C, Schmidinger M, Algaba F, Patard JJ, Khoo V, et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of oncology. 2014;25:iii49-56.
  12. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. New England Journal of Medicine. 2015;373(19):1803-13.
  13. Al-Shakarchi W, Saber Y, Merkhan M, Mustafa Y. Acute toxicity of coumacines: an in vivo study. Georgian Medical News. 2023; 1(338):126-31.
  14. Al-Shakarchi W, Saber Y, Merkhan MM, Mustafa YF. Sub Chronic Toxicity Study of Coumacines. Pharmacognosy Journal. 2023;15(1).
  15. Ilie M, Khambata-Ford S, Copie-Bergman C, Huang L, Juco J, Hofman V, et al. Use of the 22C3 anti–PD-L1 antibody to determine PD-L1 expression in multiple automated immunohistochemistry platforms. PLoSOne. 2017;12(8):e0183023.
  16. Majeed MI, Mammdoh JK, Al-Allaf LI. Effect of montelukast on healing of induced oral ulcer in rats. MMSL. 2023;92(4):348-55.
  17. Chipollini J, da Costa WH, Werneck da Cunha I, de Almeida e Paula F, Guilherme O, Salles P, et al. Prognostic value of PD-L1 expression for surgically treated localized renal cell carcinoma: implications for risk stratification and adjuvant therapies. Therapeutic Advances in Urology. 2019;11:1756287219882600.
  18. Kammerer-Jacquet SF, Deleuze A, Saout J, Mathieu R, Laguerre B, Verhoest G, et al. Targeting the PD-1/PD-L1 pathway in renal cell carcinoma. International Journal of Molecular Sciences. 2019;20(7):1692.
  19. Lipson EJ, Sharfman WH, Drake CG, Wollner I, Taube JM, Anders RA, et al. Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody. Clinical Cancer Research. 2013;19(2):462-8.
  20. Stenzel PJ, Schindeldecker M, Tagscherer KE, Foersch S, Herpel E, Hohenfellner M, et al. Prognostic and predictive value of tumor-infiltrating leukocytes and of immune checkpoint molecules PD1 and PDL1 in clear cell renal cell carcinoma. Translational oncology. 2020;13(2):336-45.
  21. Aeppli S, Eboulet E, Eisen T, Escudier B, Fischer S, Larkin J, et al. Impact of COVID-19 pandemic on treatment patterns in metastatic clear cell renal cell carcinoma. ESMO open. 2020;5:e000852.
  22. Ali RM, Muhealdeen DN, Fakhralddin SS, Bapir R, Tahir SH, Rashid RJ, et al. Prognostic factors in renal cell carcinoma: A single‑center study. Molecular and Clinical Oncology. 2023;19(3):1-7.
  23. Kumar B, Ghosh A, Datta C, Pal DK. Role of PDL1 as a prognostic marker in renal cell carcinoma: a prospective observational study in eastern India. Therapeutic Advances in Urology. 2019;11:1756287219868859.
  24. Elkhodary HS, Nasr KE, Ahmed SH, Shakweer MM, Ezz-Eldin MM. Clinicopathological correlation and prognostic value of PD-L1 expression in renal cell carcinoma. Immunopathologia Persa. 2022;8(2):e30329-.
  25. Tabriz HM, Nazar E, Akhlaghi N, Javadi AE. Expression of Programmed Death-1 Ligand in Renal Cell Carcinoma and Its Relationship with Pathologic Findings and Disease-Free Survival. Nephro-Urology Monthly. 2022;14(4).
  26. Walter B, Gil S, Naizhen X, Kruhlak MJ, Linehan WM, Srinivasan R, et al. Determination of the expression of PD-L1 in the morphologic spectrum of renal cell carcinoma. Journal of Cancer. 2020;11(12):3596.
  27. Ezenwa EV, Tan YH. Ethnic variation of the histological subtypes of renal cell carcinoma in Singapore. African Journal of Urology. 2014;20(4):184-8.
  28. Abdullah HA, Hashim AY, Al-azzo NS. Renal cell carcinoma: A clinicopathological study in Nineveh provinice. The Arab board for Health specialization. The Scientific Council of Histopathology.
  29. Yousif A, Mohsin SA. malignant renal tumors in Iraq (clinical and epidemiological study). University of Thi-Qar Journal Of Medicine. 2011;5(2):117-26.
  30. Kosary CL. SEER Cancer Stat Facts: Kidney and Renal Pelvis Cancer. National Cancer Institute. Bethesda, MD, 2021.
  31. Ljungberg B, Bensalah K, Canfield S, Dabestani S, Hofmann F, Hora M, et al. EAU guidelines on renal cell carcinoma: 2014 update. European urology. 2015;67(5):913-24.
  32. Mohamed AH, Abdullahi IM, Eraslan A, Mohamud HA, Gur M. Epidemiological and Histopathological Characteristics of Renal Cell Carcinoma in Somalia. Cancer Management and Research. 2022:1837-44.
  33. Avakoudjo DG, Hounnasso PP, Traore MT, Natchagandé G, Pare AK, Tore-Sanni R, et al. Experience with managing solid kidney tumours in Cotonou, Benin Republic. Journal of the West African College of Surgeons. 2014;4(4):100.
  34. Salako AA, Badmus TA, Badmos KB, David RA, Laoye A, Akinbola IA, et al. Renal cell carcinoma in a semi-urban population of south-western Nigeria. East African Medical Journal. 2017 Apr 18;94(1):37-43.
  35. Weikert S, Ljungberg B. Contemporary epidemiology of renal cell carcinoma: perspectives of primary prevention. World Journal of Urology. 2010;28:247-52.
  36. Alawad SA, Alghamdi MH, Alharbi MG, Addar A, Al Khayal AM, Alasker A. Characteristics of renal cell carcinoma in Saudi patients below the age of 50 years. Urology Annals. 2022;14(1):15.
  37. Inamura K. Renal cell tumors: understanding their molecular pathological epidemiology and the 2016 WHO classification. International journal of molecular sciences. 2017;18(10):2195.
  38. Dudani S, de Velasco G, Wells JC, Gan CL, Donskov F, Porta C, et al. Evaluation of clear cell, papillary, and chromophobe renal cell carcinoma metastasis sites and association with survival. JAMA network open. 2021;4(1):e2021869-.
  39. Mahasin SZ, Aloudah N, Al-Surimi K, Alkhateeb SS. Epidemiology profile of renal cell carcinoma: A 10-year patients' experience at King Abdulaziz medical city, National Guard Health Affairs, Saudi Arabia. Urology Annals. 2018;10(1):59.
  40. Patel HD, Gupta M, Joice GA, Srivastava A, Alam R, Allaf ME, et al. Clinical stage migration and survival for renal cell carcinoma in the United States. European Urology Oncology. 2019;2(4):343-8.
  41. Dagher J, Delahunt B, Rioux‐Leclercq N, Egevad L, Srigley JR, Coughlin G, et al. Clear cell renal cell carcinoma: validation of World Health Organization/International Society of Urological Pathology grading. 2017;71(6):918-25.
  42. Guo S, Yao K, He X, Wu S, Ye Y, Chen J, et al. Prognostic significance of laterality in renal cell carcinoma: a population‐based study from the surveillance, epidemiology, and end results (SEER) database. Cancer medicine. 2019;8(12):5629-37.
  43. Mandrekar S, Amoncar S, Raiturkar SP, Prabhudesai M, Pinto RW. A histopathological study of renal cell carcinoma at a tertiary care hospital. Indian J Pathol Oncol. 2021;8:193-7.
  44. Devendar K, Murugesan M, Ciancio G, Soloway MS. Tumor thrombus involving the inferior vena cava in renal malignancy: is there a difference in clinical presentation and outcome among right and left side tumors?. International Braz J Urol. 2009;35:652-7.
  45. Al Aradi A, Al Rashed AA, Mubarak M, Hasan O, Al Arayedh A, Isa QM, et al. Renal Carcinoma Patterns and Prevalence in Bahrain: A Descriptive Study. Cureus. 2022;14(11).
  46. Leite KR, Reis ST, Junior JP, Zerati M, Gomes DD, Camara-Lopes LH, et al. PD-L1 expression in renal cell carcinoma clear cell type is related to unfavorable prognosis. Diagnostic pathology. 2015;10(1):1-6.
  47. Möller K, Fraune C, Blessin NC, Lennartz M, Kluth M, Hube-Magg C, et al. Tumor cell PD-L1 expression is a strong predictor of unfavorable prognosis in immune checkpoint therapy-naive clear cell renal cell cancer. International Urology and Nephrology. 2021:1-1.
  48. Chandrasekaran D, Sundaram S, Kadhiresan N, Padmavathi R. Programmed death ligand 1; An immunotarget for renal cell carcinoma. Asian Pacific Journal of Cancer Prevention. 2019;20(10):2951.
  49. Callea M, Albiges L, Gupta M, Cheng SC, Genega EM, Fay AP, et al. Differential expression of PD-L1 between primary and metastatic sites in clear-cell renal cell carcinoma. Cancer immunology research. 2015;3(10):1158-64.
  50. Joseph RW, Millis SZ, Carballido EM, Bryant D, Gatalica Z, Reddy S, et al. PD-1 and PD-L1 expression in renal cell carcinoma with sarcomatoid differentiation. Cancer immunology research. 2015;3(12):1303-7.