Implications of Programmed Death Ligand-1 Positivity in Non-Clear Cell Renal Cell Carcinoma

Main Article Content

Juan Chipollini
Mounsif Azizi
Charles C. Peyton
Dominic H. Tang
Jasreman Dhillon
Philippe E. Spiess

Keywords

Non-Clear Cell Renal Cell Carcinoma, Prognosis, Programmed Death Ligand-1, renal cell cancer, tumor marker

Abstract

The purpose of this study was to assess the prognostic value of programmed death ligand-1 (PD-L1) positivity in a non-clear cell renal cell carcinoma (non-ccRCC) cohort. PD-L1 expression was evaluated by immunohistochemistry (IHC) using formalin-fixed paraffin-embedded (FFPE) specimens from 45 non-ccRCC patients with available tissue. PD-L1 positivity was defined as ≥1% of staining. Histopathological characteristics and oncological outcomes were correlated to PD-L1 expression. Cancer-specific survival (CSS) and recurrence-free survival (RFS) stratified by PD-L1 status were estimated using the Kaplan–Meier method. Median age was 58 years and median follow-up was 40 months. Non-ccRCC subtypes included sarcomatoid (n = 9), rhabdoid (n = 6), medullary (n = 2), Xp11.2 translocation (n = 2), collecting duct (n = 1), papillary type I (n = 11), and papillary type II (n = 14). PD-L1 positivity was noted in nine (20%) patients. PD-L1 positivity was significantly associated with higher Fuhrman nuclear grade (P = 0.048) and perineural invasion (P = 0.043). Five-year CSS was 73.2 and 83% for PD-L1 positive and negative tumors, respectively (P = 0.47). Five-year RFS was 55.6 and 61.5% for PD-L1 positive and negative tumors, respectively (P = 0.58). PD-L1 was expressed in a fifth of non-ccRCC cases and was associated with adverse histopathologic features. Expression of biomarkers such PD-L1 may help better risk-stratify non-ccRCC patients to guide treatment decisions and follow-up strategies.

Abstract 2184 | PDF Downloads 1002 HTML Downloads 1772 XML Downloads 1113

References

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30. https://doi.org/10.3322/caac.21332
2. Shah BK, Ghimire KB. Survival trends among patients with advanced renal cell carcinoma in the United States. Urol Int. 2015;94(2):133–6. https://doi.org/10.1159/000364951
3. Lam JS, Belldegrun AS, Pantuck AJ. Long-term outcomes of the surgical management of renal cell carcinoma. World J Urol. 2006;24(3):255–66. https://doi.org/10.1007/s00345-006-0055-5
4. Chin AI, Lam JS, Figlin RA, Belldegrun AS. Surveillance strategies for renal cell carcinoma patients following nephrectomy. Rev Urol. 2006;8(1):1–7.
5. Rosenberg SA. Interleukin 2 for patients with renal cancer. Nat Clin Pract Oncol. 2007;4(9):497. https://doi.org/10.1038/ncponc0926
6. Mann SA, Lopez-Beltran A, Massari F, Pili R, Fiorentino M, Koch MO, et al. Targeting the programmed Cell Death-1 pathway in genitourinary tumors: Current progress and future perspectives. Curr Drug Metab. 2017;18(8):700–11. https://doi.org/10.2174/1389200218666170518162500
7. Motzer RJ, Bacik J, Schwartz LH, Reuter V, Russo P, Marion S, et al. Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol. 2004;22(3):454–63. https://doi.org/10.1200/JCO.2004.06.132
8. Ball MW, Allaf ME, Drake CG. Recent advances in immunotherapy for kidney cancer. Discov Med. 2016;21(116):305–13.
9. McDermott DF, Drake CG, Sznol M, Choueiri TK, Powderly JD, Smith DC, et al. Survival, durable response, and long-term safety in patients with previously treated advanced renal cell carcinoma receiving nivolumab. J Clin Oncol. 2015;33(18):2013–20. https://doi.org/10.1200/JCO.2014.58.1041
10. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803–13. https://doi.org/10.1056/NEJMoa1510665 11. Carbognin L, Pilotto S, Milella M, Vaccaro V, Brunelli M, Calio A, et al. Differential activity of Nivolumab, Pembrolizumab and MPDL3280A according to the tumor expression of programmed death-Ligand-1 (PD-L1): Sensitivity analysis of trials in melanoma, lung and genitourinary cancers. PLoS One. 2015;10(6):e0130142. https://doi.org/10.1371/journal.pone.0130142
12. Festino L, Botti G, Lorigan P, Masucci GV, Hipp JD, Horak CE, et al. Cancer treatment with anti-PD-1/PD-L1 Agents: Is PD-L1 expression a biomarker for patient selection? Drugs. 2016;76(9):925–45. https://doi.org/10.1007/s40265-016-0588-x
13. Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992;11(11):3887–95. https://doi.org/10.1002/j.1460-2075.1992.tb05481.x
14. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704. https://doi.org/10.1146/annurev.immunol.26.021607.090331
15. McDermott DF, Atkins MB. PD-1 as a potential target in cancer therapy. Cancer Med. 2013;2(5):662–73. https://doi.org/10.1002/cam4.106
16. Thompson RH, Dong H, Lohse CM, Leibovich BC, Blute ML, Cheville JC, et al. PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. Clin Cancer Res. 2007;13(6):1757–61. https://doi.org/10.1158/1078-0432.CCR-06-2599
17. Mu CY, Huang JA, Chen Y, Chen C, Zhang XG. High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation. Med Oncol. 2011;28(3):682–8. https://doi.org/10.1007/s12032-010-9515-2
18. Kammerer-Jacquet SF, Crouzet L, Brunot A, Dagher J, Pladys A, Edeline J, et al. Independent association of PD-L1 expression with noninactivated VHL clear cell renal cell carcinoma-A finding with therapeutic potential. Int J Cancer. 2017;140(1):142–8. https://doi.org/10.1002/ijc.30429
19. Hino R, Kabashima K, Kato Y, Yagi H, Nakamura M, Honjo T, et al. Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer. 2010;116(7):1757–66. https://doi.org/10.1002/cncr.24899
20. Thompson RH, Kuntz SM, Leibovich BC, Dong H, Lohse CM, Webster WS, et al. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res. 2006;66(7):3381–5. https://doi.org/10.1158/0008-5472.CAN-05-4303
21. Thompson RH, Gillett MD, Cheville JC, Lohse CM, Dong H, Webster WS, et al. Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinoma. Cancer. 2005;104(10):2084–91. https://doi.org/10.1002/cncr.21470
22. Choueiri TK, Fay AP, Gray KP, Callea M, Ho TH, Albiges L, et al. PD-L1 expression in nonclear-cell renal cell carcinoma. Ann Oncol. 2014;25(11):2178–84. https://doi.org/10.1093/annonc/mdu445
23. Abbas M, Steffens S, Bellut M, Becker JU, Grosshennig A, Eggers H, et al. Do programmed death 1 (PD-1) and its ligand (PD-L1) play a role in patients with non-clear cell renal cell carcinoma? Med Oncol. 2016;33(6):59. https://doi.org/10.1007/s12032-016-0770-8
24. Vera-Badillo FE, Templeton AJ, Duran I, Ocana A, de Gouveia P, Aneja P, et al. Systemic therapy for non-clear cell renal cell carcinomas: A systematic review and meta-analysis. Eur Urol. 2015;67(4):740–9. https://doi.org/10.1016/j.eururo.2014.05.010