Skip to main content
Erschienen 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

verfasst von: 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

Erschienen in: Medical Oncology | Ausgabe 5/2017

Einloggen, um Zugang zu erhalten

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).
Literatur
1.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
19.
20.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
Metadaten
Titel
Prognostic significance of PD-L1 expression on tumor cells and tumor-infiltrating mononuclear cells in upper tract urothelial carcinoma
verfasst von
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
Publikationsdatum
01.05.2017
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 5/2017
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-017-0941-2

Weitere Artikel der Ausgabe 5/2017

Medical Oncology 5/2017 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.