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Published in: Medical Oncology 5/2017

01-05-2017 | Original Paper

Prognostic significance of PD-L1 expression on tumor cells and tumor-infiltrating mononuclear cells in upper tract urothelial carcinoma

Authors: Bo Zhang, Wei Yu, Xueru Feng, Zheng Zhao, Yu Fan, Yisen Meng, Shuai Hu, Yun Cui, Qun He, Hong Zhang, Dong Li, Zhisong He, Liqun Zhou, Jie Jin, Wenke Han

Published in: Medical Oncology | Issue 5/2017

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Abstract

Immunotherapy targeting the programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) pathway has shown promising results in several malignancies. However, the prognostic significance of PD-L1 expression remains unknown in patients with upper tract urothelial carcinoma (UTUC). This study aimed to evaluate PD-L1 expression and its association with clinicopathological characteristics and oncological outcomes in UTUC patients. PD-L1 expression on tumor cells and tumor-infiltrating mononuclear cells (TIMCs), and E-cadherin and N-cadherin expression on tumor cells were assessed by immunohistochemistry in a cohort of 162 patients with UTUC. Associations of PD-L1 expression on tumor cells and TIMCs with clinicopathological characteristics and cancer-specific survival (CSS) were evaluated. Out of 162 patients, 20 (12.3%) and 35 (21.6%) had positive PD-L1 expression on tumor cells and TIMCs, respectively. Decreased E-cadherin expression was associated with PD-L1 positivity on tumor cells (P = 0.048) and PD-L1 negativity on TIMCs (P = 0.033). PD-L1 expression on tumor cells was higher in patients with preoperative chronic kidney disease (CKD) stage 4–5 than in those with no CKD or CKD stage 1–3 (P = 0.011). PD-L1 was differentially expressed in tumor cells and TIMCs in UTUC. Multivariate analyses revealed that PD-L1 expression on tumor cells independently predicted shorter CSS (P = 0.012), whereas PD-L1 expression on TIMCs independently predicted longer CSS (P = 0.034).
Literature
1.
go back to reference Roupret M, Zigeuner R, Palou J, Boehle A, Kaasinen E, Sylvester R, et al. European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update. Eur Urol. 2011;59(4):584–94.CrossRefPubMed Roupret M, Zigeuner R, Palou J, Boehle A, Kaasinen E, Sylvester R, et al. European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update. Eur Urol. 2011;59(4):584–94.CrossRefPubMed
2.
go back to reference Chen CH, Dickman KG, Huang CY, Moriya M, Shun CT, Tai HC, et al. Aristolochic acid-induced upper tract urothelial carcinoma in Taiwan: clinical characteristics and outcomes. Int J Cancer. 2013;133(1):14–20.CrossRefPubMed Chen CH, Dickman KG, Huang CY, Moriya M, Shun CT, Tai HC, et al. Aristolochic acid-induced upper tract urothelial carcinoma in Taiwan: clinical characteristics and outcomes. Int J Cancer. 2013;133(1):14–20.CrossRefPubMed
3.
go back to reference Chen CY, Liao YM, Tsai WM, Kuo HC. Upper urinary tract urothelial carcinoma in eastern Taiwan: high proportion among all urothelial carcinomas and correlation with chronic kidney disease. J Formos Med Assoc Taiwan yi zhi. 2007;106(12):992–8.CrossRefPubMed Chen CY, Liao YM, Tsai WM, Kuo HC. Upper urinary tract urothelial carcinoma in eastern Taiwan: high proportion among all urothelial carcinomas and correlation with chronic kidney disease. J Formos Med Assoc Taiwan yi zhi. 2007;106(12):992–8.CrossRefPubMed
4.
go back to reference Holmang S, Johansson SL. Urothelial carcinoma of the upper urinary tract: comparison between the WHO/ISUP 1998 consensus classification and WHO 1999 classification system. Urology. 2005;66(2):274–8.CrossRefPubMed Holmang S, Johansson SL. Urothelial carcinoma of the upper urinary tract: comparison between the WHO/ISUP 1998 consensus classification and WHO 1999 classification system. Urology. 2005;66(2):274–8.CrossRefPubMed
5.
go back to reference Zigeuner R, Pummer K. Urothelial carcinoma of the upper urinary tract: surgical approach and prognostic factors. Eur Urol. 2008;53(4):720–31.CrossRefPubMed Zigeuner R, Pummer K. Urothelial carcinoma of the upper urinary tract: surgical approach and prognostic factors. Eur Urol. 2008;53(4):720–31.CrossRefPubMed
6.
go back to reference Margulis V, Shariat SF, Matin SF, Kamat AM, Zigeuner R, Kikuchi E, et al. Outcomes of radical nephroureterectomy: a series from the upper tract urothelial carcinoma collaboration. Cancer. 2009;115(6):1224–33.CrossRefPubMed Margulis V, Shariat SF, Matin SF, Kamat AM, Zigeuner R, Kikuchi E, et al. Outcomes of radical nephroureterectomy: a series from the upper tract urothelial carcinoma collaboration. Cancer. 2009;115(6):1224–33.CrossRefPubMed
7.
go back to reference Hall MC, Womack S, Sagalowsky AI, Carmody T, Erickstad MD, Roehrborn CG. Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. Urology. 1998;52(4):594–601.CrossRefPubMed Hall MC, Womack S, Sagalowsky AI, Carmody T, Erickstad MD, Roehrborn CG. Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. Urology. 1998;52(4):594–601.CrossRefPubMed
8.
go back to reference Favaretto RL, Shariat SF, Chade DC, Godoy G, Adamy A, Kaag M, et al. The effect of tumor location on prognosis in patients treated with radical nephroureterectomy at Memorial Sloan-Kettering Cancer Center. Eur Urol. 2010;58(4):574–80.CrossRefPubMedPubMedCentral Favaretto RL, Shariat SF, Chade DC, Godoy G, Adamy A, Kaag M, et al. The effect of tumor location on prognosis in patients treated with radical nephroureterectomy at Memorial Sloan-Kettering Cancer Center. Eur Urol. 2010;58(4):574–80.CrossRefPubMedPubMedCentral
9.
go back to reference Gadiot J, Hooijkaas AI, Kaiser AD, van Tinteren H, van Boven H, Blank C. Overall survival and PD-L1 expression in metastasized malignant melanoma. Cancer. 2011;117(10):2192–201.CrossRefPubMed Gadiot J, Hooijkaas AI, Kaiser AD, van Tinteren H, van Boven H, Blank C. Overall survival and PD-L1 expression in metastasized malignant melanoma. Cancer. 2011;117(10):2192–201.CrossRefPubMed
10.
go back to reference Bellmunt J, Mullane SA, Werner L, Fay AP, Callea M, Leow JJ, 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):812–7.CrossRefPubMed Bellmunt J, Mullane SA, Werner L, Fay AP, Callea M, Leow JJ, 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):812–7.CrossRefPubMed
11.
go back to reference Qin T, Zeng YD, Qin G, Xu F, Lu JB, Fang WF, et al. High PD-L1 expression was associated with poor prognosis in 870 Chinese patients with breast cancer. Oncotarget. 2015;6(32):33972–81.PubMedPubMedCentral Qin T, Zeng YD, Qin G, Xu F, Lu JB, Fang WF, et al. High PD-L1 expression was associated with poor prognosis in 870 Chinese patients with breast cancer. Oncotarget. 2015;6(32):33972–81.PubMedPubMedCentral
12.
go back to reference Shin SJ, Jeon YK, Kim PJ, Cho YM, Koh J, Chung DH, et al. Clinicopathologic analysis of PD-L1 and PD-L2 expression in renal cell carcinoma: association with oncogenic proteins status. Ann Surg Oncol. 2015;23(2):694–702.CrossRef Shin SJ, Jeon YK, Kim PJ, Cho YM, Koh J, Chung DH, et al. Clinicopathologic analysis of PD-L1 and PD-L2 expression in renal cell carcinoma: association with oncogenic proteins status. Ann Surg Oncol. 2015;23(2):694–702.CrossRef
13.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
14.
go back to reference Cao Y, Zhang L, Kamimura Y, Ritprajak P, Hashiguchi M, Hirose S, et al. B7-H1 overexpression regulates epithelial-mesenchymal transition and accelerates carcinogenesis in skin. Can Res. 2011;71(4):1235–43.CrossRef Cao Y, Zhang L, Kamimura Y, Ritprajak P, Hashiguchi M, Hirose S, et al. B7-H1 overexpression regulates epithelial-mesenchymal transition and accelerates carcinogenesis in skin. Can Res. 2011;71(4):1235–43.CrossRef
15.
go back to reference Muramaki M, Miyake H, Terakawa T, Kusuda Y, Fujisawa M. Expression profile of E-cadherin and N-cadherin in urothelial carcinoma of the upper urinary tract is associated with disease recurrence in patients undergoing nephroureterectomy. Urology. 2011;78(6):1443 e7–12.CrossRef Muramaki M, Miyake H, Terakawa T, Kusuda Y, Fujisawa M. Expression profile of E-cadherin and N-cadherin in urothelial carcinoma of the upper urinary tract is associated with disease recurrence in patients undergoing nephroureterectomy. Urology. 2011;78(6):1443 e7–12.CrossRef
17.
go back to reference Iwai Y, Terawaki S, Honjo T. PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells. Int Immunol. 2005;17(2):133–44.CrossRefPubMed Iwai Y, Terawaki S, Honjo T. PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells. Int Immunol. 2005;17(2):133–44.CrossRefPubMed
18.
go back to reference Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. New Engl J Med. 2012;366(26):2455–65.CrossRefPubMedPubMedCentral Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. New Engl J Med. 2012;366(26):2455–65.CrossRefPubMedPubMedCentral
20.
go back to reference Carosella ED, Ploussard G, LeMaoult J, Desgrandchamps F. A systematic review of immunotherapy in urologic cancer: evolving roles for targeting of CTLA-4, PD-1/PD-L1, and HLA-G. Eur Urol. 2015;68(2):267–79.CrossRefPubMed Carosella ED, Ploussard G, LeMaoult J, Desgrandchamps F. A systematic review of immunotherapy in urologic cancer: evolving roles for targeting of CTLA-4, PD-1/PD-L1, and HLA-G. Eur Urol. 2015;68(2):267–79.CrossRefPubMed
21.
go back to reference Patel N, Arya M, Muneer A, Powles T, Sullivan M, Hines J, et al. Molecular aspects of upper tract urothelial carcinoma. Urol Oncol. 2014;32(1):28 e11–20.CrossRef Patel N, Arya M, Muneer A, Powles T, Sullivan M, Hines J, et al. Molecular aspects of upper tract urothelial carcinoma. Urol Oncol. 2014;32(1):28 e11–20.CrossRef
22.
go back to reference Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12.CrossRefPubMedPubMedCentral Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12.CrossRefPubMedPubMedCentral
23.
go back to reference Cooper WA, Tran T, Vilain RE, Madore J, Selinger CI, Kohonen-Corish M, et al. PD-L1 expression is a favorable prognostic factor in early stage non-small cell carcinoma. Lung Cancer. 2015;89(2):181–8.CrossRefPubMed Cooper WA, Tran T, Vilain RE, Madore J, Selinger CI, Kohonen-Corish M, et al. PD-L1 expression is a favorable prognostic factor in early stage non-small cell carcinoma. Lung Cancer. 2015;89(2):181–8.CrossRefPubMed
24.
go back to reference 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 the bladder. Eur J Surg Oncol. 2014;40(1):121–7.CrossRefPubMed 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 the bladder. Eur J Surg Oncol. 2014;40(1):121–7.CrossRefPubMed
25.
go back to reference Inman BA, Sebo TJ, Frigola X, Dong H, Bergstralh EJ, Frank I, et al. PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer. 2007;109(8):1499–505.CrossRefPubMed Inman BA, Sebo TJ, Frigola X, Dong H, Bergstralh EJ, Frank I, et al. PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer. 2007;109(8):1499–505.CrossRefPubMed
26.
go back to reference Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34.CrossRefPubMedPubMedCentral Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34.CrossRefPubMedPubMedCentral
27.
go back to reference Keir ME, Liang SC, Guleria I, Latchman YE, Qipo A, Albacker LA, et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. J Exp Med. 2006;203(4):883–95.CrossRefPubMedPubMedCentral Keir ME, Liang SC, Guleria I, Latchman YE, Qipo A, Albacker LA, et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. J Exp Med. 2006;203(4):883–95.CrossRefPubMedPubMedCentral
29.
go back to reference Okazaki T, Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol. 2007;19(7):813–24.CrossRefPubMed Okazaki T, Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol. 2007;19(7):813–24.CrossRefPubMed
30.
go back to reference Lowrance WT, Ordonez J, Udaltsova N, Russo P, Go AS. CKD and the risk of incident cancer. J Am Soc Nephrol JASN. 2014;25(10):2327–34.CrossRefPubMed Lowrance WT, Ordonez J, Udaltsova N, Russo P, Go AS. CKD and the risk of incident cancer. J Am Soc Nephrol JASN. 2014;25(10):2327–34.CrossRefPubMed
31.
go back to reference Wang Y, Wang H, Zhao Q, Xia Y, Hu X, Guo J. PD-L1 induces epithelial-to-mesenchymal transition via activating SREBP-1c in renal cell carcinoma. Med Oncol. 2015;32(8):212.CrossRefPubMed Wang Y, Wang H, Zhao Q, Xia Y, Hu X, Guo J. PD-L1 induces epithelial-to-mesenchymal transition via activating SREBP-1c in renal cell carcinoma. Med Oncol. 2015;32(8):212.CrossRefPubMed
32.
go back to reference Alsuliman A, Colak D, Al-Harazi O, Fitwi H, Tulbah A, Al-Tweigeri T, et al. Bidirectional crosstalk between PD-L1 expression and epithelial to mesenchymal transition: significance in claudin-low breast cancer cells. Mol Cancer. 2015;14:149.CrossRefPubMedPubMedCentral Alsuliman A, Colak D, Al-Harazi O, Fitwi H, Tulbah A, Al-Tweigeri T, et al. Bidirectional crosstalk between PD-L1 expression and epithelial to mesenchymal transition: significance in claudin-low breast cancer cells. Mol Cancer. 2015;14:149.CrossRefPubMedPubMedCentral
33.
go back to reference Nakanishi J, Wada Y, Matsumoto K, Azuma M, Kikuchi K, Ueda S. Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers. Cancer Immunol Immunother CII. 2007;56(8):1173–82.CrossRefPubMed Nakanishi J, Wada Y, Matsumoto K, Azuma M, Kikuchi K, Ueda S. Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers. Cancer Immunol Immunother CII. 2007;56(8):1173–82.CrossRefPubMed
34.
go back to reference Faraj SF, Munari E, Guner G, Taube J, Anders R, Hicks J, et al. Assessment of tumoral PD-L1 expression and intratumoral CD8+ T cells in urothelial carcinoma. Urology. 2015;85(3):703 e1–6.CrossRef Faraj SF, Munari E, Guner G, Taube J, Anders R, Hicks J, et al. Assessment of tumoral PD-L1 expression and intratumoral CD8+ T cells in urothelial carcinoma. Urology. 2015;85(3):703 e1–6.CrossRef
Metadata
Title
Prognostic significance of PD-L1 expression on tumor cells and tumor-infiltrating mononuclear cells in upper tract urothelial carcinoma
Authors
Bo Zhang
Wei Yu
Xueru Feng
Zheng Zhao
Yu Fan
Yisen Meng
Shuai Hu
Yun Cui
Qun He
Hong Zhang
Dong Li
Zhisong He
Liqun Zhou
Jie Jin
Wenke Han
Publication date
01-05-2017
Publisher
Springer US
Published in
Medical Oncology / Issue 5/2017
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-017-0941-2

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