Discordance of high PD-L1 expression in primary and metastatic urothelial carcinoma lesions
Immune checkpoint inhibitors (ICI) targeting PD-(L)1 are effective in select patients with advanced urothelial carcinoma (UC). High PD-L1 expression enriches for response to ICIs; however, the predictive value of PD-L1 expression is limited, which may be due in part to dynamic expression of PD-L1 in...
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| Veröffentlicht in: | Urologic oncology 2019-05, Vol.37 (5), p.299.e19-299.e25 |
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| creator | Burgess, Earle F. Livasy, Chad Hartman, Aaron Robinson, Myra M. Symanowski, James Naso, Caroline Doherty, Shannon Guerrieri, Renato Riggs, Stephen Grigg, Claud M. Clark, Peter E. Raghavan, Derek |
| description | Immune checkpoint inhibitors (ICI) targeting PD-(L)1 are effective in select patients with advanced urothelial carcinoma (UC). High PD-L1 expression enriches for response to ICIs; however, the predictive value of PD-L1 expression is limited, which may be due in part to dynamic expression of PD-L1 in the tumor environment. We sought to characterize PD-L1 expression in primary UC and paired metastatic lesions to gain insight into the potential discordance of tumor PD-L1 expression during the metastatic process. Materials and methods: Immunohistochemical staining for PD-L1 using the SP-142 antibody was performed on primary tumors and matched metastatic specimens in 77 evaluable subjects with advanced UC. Immunohistochemical staining was scored for the percentage of cells positive ( |
| doi_str_mv | 10.1016/j.urolonc.2019.01.002 |
| format | Article |
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High PD-L1 expression enriches for response to ICIs; however, the predictive value of PD-L1 expression is limited, which may be due in part to dynamic expression of PD-L1 in the tumor environment. We sought to characterize PD-L1 expression in primary UC and paired metastatic lesions to gain insight into the potential discordance of tumor PD-L1 expression during the metastatic process. Materials and methods: Immunohistochemical staining for PD-L1 using the SP-142 antibody was performed on primary tumors and matched metastatic specimens in 77 evaluable subjects with advanced UC. Immunohistochemical staining was scored for the percentage of cells positive (<5%, ≥5%) in tumor cell (TC) and immune cell (IC) compartments. Correlation of PD-L1 expression in TCs and ICs was estimated using Spearman's correlation coefficients (rho, ρ). Cohen's kappa statistics (κ) were utilized to assess the agreement in PD-L1 expression between groups. Results: High (≥5%) PD-L1 expression in primary and metastatic biopsies, respectively, was observed in 6.0% and 7.7% of TCs and in 14.5% and 11.5% of ICs. IC PD-L1 expression in primary tumors was not correlated with IC PD-L1 expression in paired metastatic lesions (ρ = 0.05, P = 0.67) and there was poor agreement in high expression rates between primary and metastatic lesions in the IC compartment (κ= 0.086). Conclusion: High PD-L1 IC expression is temporally and spatially discordant between primary and metastatic UC lesions. Future studies of PD-(L)1 targeted therapies in patients with metastatic UC may benefit from use of fresh biopsies of metastatic lesions to define PD-L1 expression when feasible.</description><identifier>ISSN: 1078-1439</identifier><identifier>EISSN: 1873-2496</identifier><identifier>DOI: 10.1016/j.urolonc.2019.01.002</identifier><identifier>PMID: 30660491</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Atezolizumab ; B7-H1 Antigen - biosynthesis ; Bladder cancer ; Carcinoma, Transitional Cell - metabolism ; Carcinoma, Transitional Cell - secondary ; Female ; Humans ; Immune checkpoint inhibitor ; Male ; PD-(L)1 ; Retrospective Studies ; SP142 ; Urinary Bladder Neoplasms - metabolism ; Urinary Bladder Neoplasms - pathology ; Urothelial carcinoma</subject><ispartof>Urologic oncology, 2019-05, Vol.37 (5), p.299.e19-299.e25</ispartof><rights>2019</rights><rights>Copyright © 2019. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-28166aaa8e28f4072ca8d51c91d6806d13fcd73f0b434667196424a8677329193</citedby><cites>FETCH-LOGICAL-c365t-28166aaa8e28f4072ca8d51c91d6806d13fcd73f0b434667196424a8677329193</cites><orcidid>0000-0003-4293-4680</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S107814391930002X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30660491$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Burgess, Earle F.</creatorcontrib><creatorcontrib>Livasy, Chad</creatorcontrib><creatorcontrib>Hartman, Aaron</creatorcontrib><creatorcontrib>Robinson, Myra M.</creatorcontrib><creatorcontrib>Symanowski, James</creatorcontrib><creatorcontrib>Naso, Caroline</creatorcontrib><creatorcontrib>Doherty, Shannon</creatorcontrib><creatorcontrib>Guerrieri, Renato</creatorcontrib><creatorcontrib>Riggs, Stephen</creatorcontrib><creatorcontrib>Grigg, Claud M.</creatorcontrib><creatorcontrib>Clark, Peter E.</creatorcontrib><creatorcontrib>Raghavan, Derek</creatorcontrib><title>Discordance of high PD-L1 expression in primary and metastatic urothelial carcinoma lesions</title><title>Urologic oncology</title><addtitle>Urol Oncol</addtitle><description>Immune checkpoint inhibitors (ICI) targeting PD-(L)1 are effective in select patients with advanced urothelial carcinoma (UC). High PD-L1 expression enriches for response to ICIs; however, the predictive value of PD-L1 expression is limited, which may be due in part to dynamic expression of PD-L1 in the tumor environment. We sought to characterize PD-L1 expression in primary UC and paired metastatic lesions to gain insight into the potential discordance of tumor PD-L1 expression during the metastatic process. Materials and methods: Immunohistochemical staining for PD-L1 using the SP-142 antibody was performed on primary tumors and matched metastatic specimens in 77 evaluable subjects with advanced UC. Immunohistochemical staining was scored for the percentage of cells positive (<5%, ≥5%) in tumor cell (TC) and immune cell (IC) compartments. Correlation of PD-L1 expression in TCs and ICs was estimated using Spearman's correlation coefficients (rho, ρ). Cohen's kappa statistics (κ) were utilized to assess the agreement in PD-L1 expression between groups. Results: High (≥5%) PD-L1 expression in primary and metastatic biopsies, respectively, was observed in 6.0% and 7.7% of TCs and in 14.5% and 11.5% of ICs. IC PD-L1 expression in primary tumors was not correlated with IC PD-L1 expression in paired metastatic lesions (ρ = 0.05, P = 0.67) and there was poor agreement in high expression rates between primary and metastatic lesions in the IC compartment (κ= 0.086). Conclusion: High PD-L1 IC expression is temporally and spatially discordant between primary and metastatic UC lesions. Future studies of PD-(L)1 targeted therapies in patients with metastatic UC may benefit from use of fresh biopsies of metastatic lesions to define PD-L1 expression when feasible.</description><subject>Atezolizumab</subject><subject>B7-H1 Antigen - biosynthesis</subject><subject>Bladder cancer</subject><subject>Carcinoma, Transitional Cell - metabolism</subject><subject>Carcinoma, Transitional Cell - secondary</subject><subject>Female</subject><subject>Humans</subject><subject>Immune checkpoint inhibitor</subject><subject>Male</subject><subject>PD-(L)1</subject><subject>Retrospective Studies</subject><subject>SP142</subject><subject>Urinary Bladder Neoplasms - metabolism</subject><subject>Urinary Bladder Neoplasms - pathology</subject><subject>Urothelial carcinoma</subject><issn>1078-1439</issn><issn>1873-2496</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkD9PHDEQxa0oCAjwERK5pNnFY_u8doUi_iSRToKCVCksY8_mfNpdH_ZeRL49Pt2FNtVM8d68eT9CPgNrgYG6WrfbnIY0-ZYzMC2DljH-gZyC7kTDpVEf68463YAU5oR8KmXNGEgNcExOBFOKSQOn5NdtLD7l4CaPNPV0FX-v6ONtswSKr5uMpcQ00TjRTY6jy3-pmwIdcXZldnP0tD4xr3CIbqDeZR-nNDo64M5VzslR74aCF4d5Rn7e3z3dfG-WD99-3HxdNl6oxdxwDUo55zRy3UvWce90WIA3EJRmKoDofehEz56lkEp1YJTk0mnVdYIbMOKMXO7vbnJ62WKZ7VhL4TC4CdO2WA6dEXphDFTpYi_1OZWSsbeHXhaY3XG1a3vgandcLQNbuVbfl0PE9nnE8O76B7IKrvcCrEX_RMy2-IgVaogZ_WxDiv-JeAPVWYts</recordid><startdate>201905</startdate><enddate>201905</enddate><creator>Burgess, Earle F.</creator><creator>Livasy, Chad</creator><creator>Hartman, Aaron</creator><creator>Robinson, Myra M.</creator><creator>Symanowski, James</creator><creator>Naso, Caroline</creator><creator>Doherty, Shannon</creator><creator>Guerrieri, Renato</creator><creator>Riggs, Stephen</creator><creator>Grigg, Claud M.</creator><creator>Clark, Peter E.</creator><creator>Raghavan, Derek</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4293-4680</orcidid></search><sort><creationdate>201905</creationdate><title>Discordance of high PD-L1 expression in primary and metastatic urothelial carcinoma lesions</title><author>Burgess, Earle F. ; Livasy, Chad ; Hartman, Aaron ; Robinson, Myra M. ; Symanowski, James ; Naso, Caroline ; Doherty, Shannon ; Guerrieri, Renato ; Riggs, Stephen ; Grigg, Claud M. ; Clark, Peter E. ; Raghavan, Derek</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-28166aaa8e28f4072ca8d51c91d6806d13fcd73f0b434667196424a8677329193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Atezolizumab</topic><topic>B7-H1 Antigen - biosynthesis</topic><topic>Bladder cancer</topic><topic>Carcinoma, Transitional Cell - metabolism</topic><topic>Carcinoma, Transitional Cell - secondary</topic><topic>Female</topic><topic>Humans</topic><topic>Immune checkpoint inhibitor</topic><topic>Male</topic><topic>PD-(L)1</topic><topic>Retrospective Studies</topic><topic>SP142</topic><topic>Urinary Bladder Neoplasms - metabolism</topic><topic>Urinary Bladder Neoplasms - pathology</topic><topic>Urothelial carcinoma</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Burgess, Earle F.</creatorcontrib><creatorcontrib>Livasy, Chad</creatorcontrib><creatorcontrib>Hartman, Aaron</creatorcontrib><creatorcontrib>Robinson, Myra M.</creatorcontrib><creatorcontrib>Symanowski, James</creatorcontrib><creatorcontrib>Naso, Caroline</creatorcontrib><creatorcontrib>Doherty, Shannon</creatorcontrib><creatorcontrib>Guerrieri, Renato</creatorcontrib><creatorcontrib>Riggs, Stephen</creatorcontrib><creatorcontrib>Grigg, Claud M.</creatorcontrib><creatorcontrib>Clark, Peter E.</creatorcontrib><creatorcontrib>Raghavan, Derek</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Urologic oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Burgess, Earle F.</au><au>Livasy, Chad</au><au>Hartman, Aaron</au><au>Robinson, Myra M.</au><au>Symanowski, James</au><au>Naso, Caroline</au><au>Doherty, Shannon</au><au>Guerrieri, Renato</au><au>Riggs, Stephen</au><au>Grigg, Claud M.</au><au>Clark, Peter E.</au><au>Raghavan, Derek</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discordance of high PD-L1 expression in primary and metastatic urothelial carcinoma lesions</atitle><jtitle>Urologic oncology</jtitle><addtitle>Urol Oncol</addtitle><date>2019-05</date><risdate>2019</risdate><volume>37</volume><issue>5</issue><spage>299.e19</spage><epage>299.e25</epage><pages>299.e19-299.e25</pages><issn>1078-1439</issn><eissn>1873-2496</eissn><abstract>Immune checkpoint inhibitors (ICI) targeting PD-(L)1 are effective in select patients with advanced urothelial carcinoma (UC). High PD-L1 expression enriches for response to ICIs; however, the predictive value of PD-L1 expression is limited, which may be due in part to dynamic expression of PD-L1 in the tumor environment. We sought to characterize PD-L1 expression in primary UC and paired metastatic lesions to gain insight into the potential discordance of tumor PD-L1 expression during the metastatic process. Materials and methods: Immunohistochemical staining for PD-L1 using the SP-142 antibody was performed on primary tumors and matched metastatic specimens in 77 evaluable subjects with advanced UC. Immunohistochemical staining was scored for the percentage of cells positive (<5%, ≥5%) in tumor cell (TC) and immune cell (IC) compartments. Correlation of PD-L1 expression in TCs and ICs was estimated using Spearman's correlation coefficients (rho, ρ). Cohen's kappa statistics (κ) were utilized to assess the agreement in PD-L1 expression between groups. Results: High (≥5%) PD-L1 expression in primary and metastatic biopsies, respectively, was observed in 6.0% and 7.7% of TCs and in 14.5% and 11.5% of ICs. IC PD-L1 expression in primary tumors was not correlated with IC PD-L1 expression in paired metastatic lesions (ρ = 0.05, P = 0.67) and there was poor agreement in high expression rates between primary and metastatic lesions in the IC compartment (κ= 0.086). Conclusion: High PD-L1 IC expression is temporally and spatially discordant between primary and metastatic UC lesions. Future studies of PD-(L)1 targeted therapies in patients with metastatic UC may benefit from use of fresh biopsies of metastatic lesions to define PD-L1 expression when feasible.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>30660491</pmid><doi>10.1016/j.urolonc.2019.01.002</doi><orcidid>https://orcid.org/0000-0003-4293-4680</orcidid></addata></record> |
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| subjects | Atezolizumab B7-H1 Antigen - biosynthesis Bladder cancer Carcinoma, Transitional Cell - metabolism Carcinoma, Transitional Cell - secondary Female Humans Immune checkpoint inhibitor Male PD-(L)1 Retrospective Studies SP142 Urinary Bladder Neoplasms - metabolism Urinary Bladder Neoplasms - pathology Urothelial carcinoma |
| title | Discordance of high PD-L1 expression in primary and metastatic urothelial carcinoma lesions |
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