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Virchows Archiv

, Volume 474, Issue 4, pp 475–484 | Cite as

Predictive potential and need for standardization of PD-L1 immunohistochemistry

  • Spasenija Savic PrinceEmail author
  • Lukas Bubendorf
Review Article

Abstract

Checkpoint inhibitors targeting the PD-1/PD-L1 axis are a promising treatment option in several tumor types. PD-L1 expression detected by immunohistochemistry is the first clinically validated predictive biomarker for response to PD-1/PD-L1 inhibitors, though its predictive value varies significantly between tumor types. With the approval of pembrolizumab monotherapy for treatment-naïve, advanced non-small cell lung cancer, PD-L1 testing has to become broadly available in pathology laboratories. When PD-L1 testing started to be introduced in routine pathology practice, there were several open issues, which needed to be addressed in order to provide accurate results. This review will discuss the complex biological background of PD-L1 as predictive biomarker, summarize relevant clinical trials in NSCLC illustrating the origin of different PD-L1 expression cutoffs and scorings, and address issues important for PD-L1 testing including the analytical comparability of the different clinical trial-validated PD-L1 immunohistochemistry assays, the potential of laboratory-developed tests, and an overview of the different scoring algorithms.

Keywords

PD-L1 Immunohistochemistry Predictive biomarker Immunotherapy 

Notes

Author contribution

S.S.: assembly of the literature, conception, and writing of the manuscript

L.B.: assembly of the literature, conception, and writing of the manuscript

Compliance with ethical standards

Conflict of interest

S.S. attended advisory board meetings of MSD and Astra Zeneca, has a consulting role for MSD, and received speaker’s honoraria from MSD and Roche. L.B. attended advisory board meetings of Roche, MSD, Bristol-Myers Squibb, and Astra Zeneca and received financial research support from Roche and MSD. The manuscript is in compliance with ethical standards.

References

  1. 1.
    US Food and Drug Administration. Pembrolizumab prescribing information https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125514s030lbl.pdf. Accessed June 25 2018
  2. 2.
    European Medicines Agency. Summary of product characteristics: KEYTRUDA (pembrolizumab). http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003820/WC500190990.pdf. Accessed June 25 2018
  3. 3.
    US Food and Drug Administration: Nivolumab prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125554s058lbl.pdf. Accessed June 25 2018
  4. 4.
    European Medicines Agency. Summary of product characteristics: OPDIVO (nivolumab). http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003985/WC500189765.pdf. Accessed June 25 2018
  5. 5.
    US Food and Drug Administration. Atezolizumab prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761041lbl.pdf. Accessed June 25 2018
  6. 6.
    European Medicines Agency. Summary of product characteristics: Tecentriq (atezolizumab). http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004143/WC500235778.pdf. Accessed June 25 2018
  7. 7.
    US Food and Drug Administration. Durvalumab prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761069s002lbl.pdf. Accessed June 25 2018
  8. 8.
    US Food and Drug Administration. Avelumab prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761049s000lbl.pdf. Accessed June 25 2018
  9. 9.
    European Medicines Agency. Summary of product characteristics: Bavencio (avelumab). http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004338/WC500236647.pdf. Accessed June 25 2018
  10. 10.
    Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS (2014) Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 32(10):1020–1030.  https://doi.org/10.1200/JCO.2013.53.0105 CrossRefGoogle Scholar
  11. 11.
    Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbe C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Arance A, Schmidt H, Schadendorf D, Gogas H, Lundgren-Eriksson L, Horak C, Sharkey B, Waxman IM, Atkinson V, Ascierto PA (2015) Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372(4):320–330.  https://doi.org/10.1056/NEJMoa1412082 CrossRefGoogle Scholar
  12. 12.
    Melosky B, Chu Q, Juergens RA, Leighl N, Ionescu D, Tsao MS, McLeod D, Hirsh V (2018) Breaking the biomarker code: PD-L1 expression and checkpoint inhibition in advanced NSCLC. Cancer Treat Rev 65:65–77.  https://doi.org/10.1016/j.ctrv.2018.02.005 CrossRefGoogle Scholar
  13. 13.
    US Food and Drug Administration: Devices@FDA, PD-L1. https://www.accessdata.fda.gov/scripts/cdrh/devicesatfda/index.cfm. Accessed June 28 2018
  14. 14.
    Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR, Investigators K (2016) Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 375(19):1823–1833.  https://doi.org/10.1056/NEJMoa1606774 CrossRefGoogle Scholar
  15. 15.
    Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387(10027):1540–1550.  https://doi.org/10.1016/S0140-6736(15)01281-7 CrossRefGoogle Scholar
  16. 16.
    Russell-Goldman E, Kravets S, Dahlberg SE, Sholl LM, Vivero M (2018) Cytologic-histologic correlation of programmed death-ligand 1 immunohistochemistry in lung carcinomas. Cancer Cytopathol 126(4):253–263.  https://doi.org/10.1002/cncy.21973 CrossRefGoogle Scholar
  17. 17.
    Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhaufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crino L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR (2015) Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373(17):1627–1639.  https://doi.org/10.1056/NEJMoa1507643 CrossRefGoogle Scholar
  18. 18.
    Agilent: PD-L1 IHC 22C3 pharmDx Code SK006: Package Inserts. https://www.agilent.com/cs/library/packageinsert/public/P03951%20SK006%20NSCLC%20GC%20Cervical%20IFU%20Rev%2009%20FINAL.pdf. Accessed June 28 2018
  19. 19.
    Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC, Cortinovis DL, Leach J, Polikoff J, Barrios C, Kabbinavar F, Frontera OA, De Marinis F, Turna H, Lee JS, Ballinger M, Kowanetz M, He P, Chen DS, Sandler A, Gandara DR, Group OAKS (2017) Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 389(10066):255–265.  https://doi.org/10.1016/S0140-6736(16)32517-X CrossRefGoogle Scholar
  20. 20.
    Ventana: VENTANA PD-L1 (SP263) Assay Package Inserts, REF 740–4907. http://productlibrary.ventana.com/ventana_portal/OpenOverlayServlet?launchIndex=1&objectId=740-49071014737US. Accessed June 28 2018
  21. 21.
    Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, Lao CD, Wagstaff J, Schadendorf D, Ferrucci PF, Smylie M, Dummer R, Hill A, Hogg D, Haanen J, Carlino MS, Bechter O, Maio M, Marquez-Rodas I, Guidoboni M, McArthur G, Lebbe C, Ascierto PA, Long GV, Cebon J, Sosman J, Postow MA, Callahan MK, Walker D, Rollin L, Bhore R, Hodi FS, Larkin J (2017) Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 377(14):1345–1356.  https://doi.org/10.1056/NEJMoa1709684 CrossRefGoogle Scholar
  22. 22.
    Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH (2018) Safety and efficacy of Pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction Cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol 4(5):e180013.  https://doi.org/10.1001/jamaoncol.2018.0013 CrossRefGoogle Scholar
  23. 23.
    Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R (2016) Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 387(10031):1909–1920.  https://doi.org/10.1016/S0140-6736(16)00561-4 CrossRefGoogle Scholar
  24. 24.
    Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J, Plimack ER, Vaena D, Grimm MO, Bracarda S, Arranz JA, Pal S, Ohyama C, Saci A, Qu X, Lambert A, Krishnan S, Azrilevich A, Galsky MD (2017) Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol 18(3):312–322.  https://doi.org/10.1016/S1470-2045(17)30065-7 CrossRefGoogle Scholar
  25. 25.
    Massard C, Gordon MS, Sharma S, Rafii S, Wainberg ZA, Luke J, Curiel TJ, Colon-Otero G, Hamid O, Sanborn RE, O'Donnell PH, Drakaki A, Tan W, Kurland JF, Rebelatto MC, Jin X, Blake-Haskins JA, Gupta A, Segal NH (2016) Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol 34(26):3119–3125.  https://doi.org/10.1200/JCO.2016.67.9761 CrossRefGoogle Scholar
  26. 26.
    Agilent: PD-L1 IHC 28-8pharmDx Code SK005: Package Inserts. https://www.agilent.com/cs/library/packageinsert/public/P04163_rev_05_2017Sep15.pdf. Accessed June 28 2018
  27. 27.
    Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375(19):1856–1867.  https://doi.org/10.1056/NEJMoa1602252 CrossRefGoogle Scholar
  28. 28.
    Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12(4):252–264.  https://doi.org/10.1038/nrc3239 CrossRefGoogle Scholar
  29. 29.
    Chen DS, Mellman I (2017) Elements of cancer immunity and the cancer-immune set point. Nature 541(7637):321–330.  https://doi.org/10.1038/nature21349 CrossRefGoogle Scholar
  30. 30.
    Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, Carter SL, Stewart C, Mermel CH, Roberts SA, Kiezun A, Hammerman PS, McKenna A, Drier Y, Zou L, Ramos AH, Pugh TJ, Stransky N, Helman E, Kim J, Sougnez C, Ambrogio L, Nickerson E, Shefler E, Cortes ML, Auclair D, Saksena G, Voet D, Noble M, DiCara D, Lin P, Lichtenstein L, Heiman DI, Fennell T, Imielinski M, Hernandez B, Hodis E, Baca S, Dulak AM, Lohr J, Landau DA, Wu CJ, Melendez-Zajgla J, Hidalgo-Miranda A, Koren A, McCarroll SA, Mora J, Crompton B, Onofrio R, Parkin M, Winckler W, Ardlie K, Gabriel SB, Roberts CWM, Biegel JA, Stegmaier K, Bass AJ, Garraway LA, Meyerson M, Golub TR, Gordenin DA, Sunyaev S, Lander ES, Getz G (2013) Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499(7457):214–218.  https://doi.org/10.1038/nature12213 CrossRefGoogle Scholar
  31. 31.
    Kerr KM, Hirsch FR (2016) Programmed death ligand-1 immunohistochemistry: friend or foe? Arch Pathol Lab Med 140(4):326–331.  https://doi.org/10.5858/arpa.2015-0522-SA CrossRefGoogle Scholar
  32. 32.
    Sholl LM, Aisner DL, Allen TC, Beasley MB, Borczuk AC, Cagle PT, Capelozzi V, Dacic S, Hariri L, Kerr KM, Lantuejoul S, Mino-Kenudson M, Raparia K, Rekhtman N, Roy-Chowdhuri S, Thunnissen E, Tsao MS, Yatabe Y, Members of Pulmonary Pathology S (2016) Programmed death ligand-1 immunohistochemistry--a new challenge for pathologists: a perspective from members of the pulmonary pathology Society. Arch Pathol Lab Med 140(4):341–344.  https://doi.org/10.5858/arpa.2015-0506-SA CrossRefGoogle Scholar
  33. 33.
    Sunshine J, Taube JM (2015) PD-1/PD-L1 inhibitors. Curr Opin Pharmacol 23:32–38.  https://doi.org/10.1016/j.coph.2015.05.011 CrossRefGoogle Scholar
  34. 34.
    NCCN Clinical Practice Guidelines in Oncology. Non-Small Cell Lung Cancer. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed June 28 2018
  35. 35.
    Langer CJ, Gadgeel SM, Borghaei H, Papadimitrakopoulou VA, Patnaik A, Powell SF, Gentzler RD, Martins RG, Stevenson JP, Jalal SI, Panwalkar A, Yang JC, Gubens M, Sequist LV, Awad MM, Fiore J, Ge Y, Raftopoulos H, Gandhi L, investigators K (2016) Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol 17(11):1497–1508.  https://doi.org/10.1016/S1470-2045(16)30498-3 CrossRefGoogle Scholar
  36. 36.
    Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR (2015) Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373(2):123–135.  https://doi.org/10.1056/NEJMoa1504627 CrossRefGoogle Scholar
  37. 37.
    Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Ozguroglu M, Investigators P (2017) Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med 377(20):1919–1929.  https://doi.org/10.1056/NEJMoa1709937 CrossRefGoogle Scholar
  38. 38.
    Fehrenbacher L, von Pawel J, Park K, Rittmeyer A, Gandara DR, Ponce Aix S, Han JY, Gadgeel SM, Hida T, Cortinovis DL, Cobo M, Kowalski DM, De Marinis F, Gandhi M, Danner B, Matheny C, Kowanetz M, He P, Felizzi F, Patel H, Sandler A, Ballinger M, Barlesi F (2018) Updated efficacy analysis including secondary population results for OAK: a randomized phase III study of atezolizumab vs docetaxel in patients with previously treated advanced non-small cell lung cancer. J Thorac Oncol 13:1156–1170.  https://doi.org/10.1016/j.jtho.2018.04.039 CrossRefGoogle Scholar
  39. 39.
    Buttner R, Gosney JR, Skov BG, Adam J, Motoi N, Bloom KJ, Dietel M, Longshore JW, Lopez-Rios F, Penault-Llorca F, Viale G, Wotherspoon AC, Kerr KM, Tsao MS (2017) Programmed death-ligand 1 immunohistochemistry testing: a review of analytical assays and clinical implementation in non-small-cell lung cancer. J Clin Oncol 35(34):3867–3876.  https://doi.org/10.1200/JCO.2017.74.7642 CrossRefGoogle Scholar
  40. 40.
    Scheel AH, Dietel M, Heukamp LC, Johrens K, Kirchner T, Reu S, Ruschoff J, Schildhaus HU, Schirmacher P, Tiemann M, Warth A, Weichert W, Fischer RN, Wolf J, Buettner R (2016) Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. Mod Pathol 29(10):1165–1172.  https://doi.org/10.1038/modpathol.2016.117 CrossRefGoogle Scholar
  41. 41.
    Ratcliffe MJ, Sharpe A, Midha A, Barker C, Scott M, Scorer P, Al-Masri H, Rebelatto MC, Walker J (2017) Agreement between programmed cell death ligand-1 diagnostic assays across multiple protein expression cutoffs in non-small cell lung cancer. Clin Cancer Res 23(14):3585–3591.  https://doi.org/10.1158/1078-0432.CCR-16-2375 CrossRefGoogle Scholar
  42. 42.
    Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, Homer R, West WW, Wu H, Roden AC, Fujimoto J, Yu H, Anders R, Kowalewski A, Rivard C, Rehman J, Batenchuk C, Burns V, Hirsch FR, Wistuba II (2017) A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer. JAMA Oncol 3(8):1051–1058.  https://doi.org/10.1001/jamaoncol.2017.0013 CrossRefGoogle Scholar
  43. 43.
    Hirsch FR, McElhinny A, Stanforth D, Ranger-Moore J, Jansson M, Kulangara K, Richardson W, Towne P, Hanks D, Vennapusa B, Mistry A, Kalamegham R, Averbuch S, Novotny J, Rubin E, Emancipator K, McCaffery I, Williams JA, Walker J, Longshore J, Tsao MS, Kerr KM (2017) PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol 12(2):208–222.  https://doi.org/10.1016/j.jtho.2016.11.2228 CrossRefGoogle Scholar
  44. 44.
    Tsao MS, Kerr KM, Kockx M, Beasley MB, Borczuk AC, Botling J, Bubendorf L, Chirieac L, Chen G, Chou TY, Chung JH, Dacic S, Lantuejoul S, Mino-Kenudson M, Moreira AL, Nicholson AG, Noguchi M, Pelosi G, Poleri C, Russell PA, Sauter J, Thunnissen E, Wistuba I, Yu H, Wynes MW, Pintilie M, Yatabe Y, Hirsch FR (2018) PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of Blueprint phase 2 project. J Thorac Oncol.  https://doi.org/10.1016/j.jtho.2018.05.013
  45. 45.
    Adam J, Le Stang N, Rouquette I, Cazes A, Badoual C, Pinot-Roussel H, Tixier L, Danel C, Damiola F, Damotte D, Penault-Llorca F, Lantuejoul S (2018) Multicenter harmonization study for PD-L1 IHC testing in non-small-cell lung cancer. Ann Oncol 29(4):953–958.  https://doi.org/10.1093/annonc/mdy014 CrossRefGoogle Scholar
  46. 46.
    Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L, Investigators K (2015) Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 372(21):2018–2028.  https://doi.org/10.1056/NEJMoa1501824 CrossRefGoogle Scholar
  47. 47.
    Chan AWH, Tong JHM, Kwan JSH, Chow C, Chung LY, Chau SL, Lung RWM, Ng CSH, Wan IYP, Mok TSK, To KF (2018) Assessment of programmed cell death ligand-1 expression by 4 diagnostic assays and its clinicopathological correlation in a large cohort of surgical resected non-small cell lung carcinoma. Mod Pathol.  https://doi.org/10.1038/s41379-018-0053-3
  48. 48.
    Hendry S, Byrne DJ, Wright GM, Young RJ, Sturrock S, Cooper WA, Fox SB (2018) Comparison of four PD-L1 immunohistochemical assays in lung cancer. J Thorac Oncol 13(3):367–376.  https://doi.org/10.1016/j.jtho.2017.11.112 CrossRefGoogle Scholar
  49. 49.
    Cooper WA, Russell PA, Cherian M, Duhig EE, Godbolt D, Jessup PJ, Khoo C, Leslie C, Mahar A, Moffat DF, Sivasubramaniam V, Faure C, Reznichenko A, Grattan A, Fox SB (2017) Intra- and interobserver reproducibility assessment of PD-L1 biomarker in non-small cell lung cancer. Clin Cancer Res 23(16):4569–4577.  https://doi.org/10.1158/1078-0432.CCR-17-0151 CrossRefGoogle Scholar
  50. 50.
    Scheel AH, Baenfer G, Baretton G, Dietel M, Diezko R, Henkel T, Heukamp LC, Jasani B, Johrens K, Kirchner T, Lasitschka F, Petersen I, Reu S, Schildhaus HU, Schirmacher P, Schwamborn K, Sommer U, Stoss O, Tiemann M, Warth A, Weichert W, Wolf J, Buttner R, Ruschoff J (2018) Interlaboratory concordance of PD-L1 immunohistochemistry for non-small-cell lung cancer. Histopathology 72(3):449–459.  https://doi.org/10.1111/his.13375 CrossRefGoogle Scholar
  51. 51.
    Neuman T, London M, Kania-Almog J, Litvin A, Zohar Y, Fridel L, Sandbank J, Barshak I, Vainer GW (2016) A harmonization study for the use of 22C3 PD-L1 mmmunohistochemical staining on Ventana’s platform. J Thorac Oncol 11(11):1863–1868.  https://doi.org/10.1016/j.jtho.2016.08.146 CrossRefGoogle Scholar
  52. 52.
    Ilie M, Khambata-Ford S, Copie-Bergman C, Huang L, Juco J, Hofman V, Hofman P (2017) Use of the 22C3 anti-PD-L1 antibody to determine PD-L1 expression in multiple automated immunohistochemistry platforms. PLoS One 12(8):e0183023.  https://doi.org/10.1371/journal.pone.0183023 CrossRefGoogle Scholar
  53. 53.
    Roge R, Vyberg M, Nielsen S (2017) Accurate PD-L1 protocols for non-small cell lung cancer can be developed for automated staining platforms with clone 22C3. Appl Immunohistochem Mol Morphol 25(6):381–385.  https://doi.org/10.1097/PAI.0000000000000534 CrossRefGoogle Scholar
  54. 54.
    Gaule P, Smithy JW, Toki M, Rehman J, Patell-Socha F, Cougot D, Collin P, Morrill P, Neumeister V, Rimm DL (2016) A quantitative comparison of antibodies to programmed cell death 1 ligand 1. JAMA Oncol 3:256.  https://doi.org/10.1001/jamaoncol.2016.3015 CrossRefGoogle Scholar
  55. 55.
    Fitzgibbons PL, Bradley LA, Fatheree LA, Alsabeh R, Fulton RS, Goldsmith JD, Haas TS, Karabakhtsian RG, Loykasek PA, Marolt MJ, Shen SS, Smith AT, Swanson PE, College of American Pathologists P, Laboratory Quality C (2014) Principles of analytic validation of immunohistochemical assays: guideline from the College of American Pathologists Pathology and Laboratory Quality Center. Arch Pathol Lab Med 138(11):1432–1443.  https://doi.org/10.5858/arpa.2013-0610-CP CrossRefGoogle Scholar
  56. 56.
    Thunnissen E, de Langen AJ, Smit EF (2017) PD-L1 IHC in NSCLC with a global and methodological perspective. Lung Cancer 113:102–105.  https://doi.org/10.1016/j.lungcan.2017.09.010 CrossRefGoogle Scholar
  57. 57.
    NordiQC. Recommended protocols - PD-L1. http://www.nordiqc.org/recommended.php?epitope_id=102. Accessed June 25 2018
  58. 58.
    NordiQC: PD-L1, see assessments Run C1, C2 and C3. http://www.nordiqc.org/epitope.php?id=102. Accessed June 28 2018
  59. 59.
    Jain D, Mathur SR, Iyer VK (2014) Cell blocks in cytopathology: a review of preparative methods, utility in diagnosis and role in ancillary studies. Cytopathology 25(6):356–371.  https://doi.org/10.1111/cyt.12174 Google Scholar
  60. 60.
    Denda T, Kamoshida S, Kawamura J, Harada K, Kawai K, Kuwao S (2012) Optimal antigen retrieval for ethanol-fixed cytologic smears. Cancer Cytopathol 120(3):167–176.  https://doi.org/10.1002/cncy.21192 CrossRefGoogle Scholar
  61. 61.
    Skov BG, Skov T (2017) Paired comparison of PD-L1 expression on cytologic and histologic specimens from malignancies in the lung assessed with PD-L1 IHC 28-8pharmDx and PD-L1 IHC 22C3pharmDx. Appl Immunohistochem Mol Morphol 25(7):453–459.  https://doi.org/10.1097/PAI.0000000000000540 CrossRefGoogle Scholar
  62. 62.
    Heymann JJ, Bulman WA, Swinarski D, Pagan CA, Crapanzano JP, Haghighi M, Fazlollahi L, Stoopler MB, Sonett JR, Sacher AG, Shu CA, Rizvi NA, Saqi A (2017) PD-L1 expression in non-small cell lung carcinoma: comparison among cytology, small biopsy, and surgical resection specimens. Cancer Cytopathol 125(12):896–907.  https://doi.org/10.1002/cncy.21937 CrossRefGoogle Scholar
  63. 63.
    Ilie M, Juco J, Huang L, Hofman V, Khambata-Ford S, Hofman P (2018) Use of the 22C3 anti-programmed death-ligand 1 antibody to determine programmed death-ligand 1 expression in cytology samples obtained from non-small cell lung cancer patients. Cancer Cytopathol 126(4):264–274.  https://doi.org/10.1002/cncy.21977 CrossRefGoogle Scholar
  64. 64.
    Noll B, Wang WL, Gong Y, Zhao J, Kalhor N, Prieto V, Staerkel G, Roy-Chowdhuri S (2018) Programmed death ligand 1 testing in non-small cell lung carcinoma cytology cell block and aspirate smear preparations. Cancer Cytopathol 126(5):342–352.  https://doi.org/10.1002/cncy.21987 CrossRefGoogle Scholar
  65. 65.
    Ventana: VENTANA PD-L1 (SP142) Assay Package Inserts, REF 740–4859. http://productlibrary.ventana.com/ventana_portal/OpenOverlayServlet?launchIndex=1&objectId=740-48591015005US. Accessed June 28 2018
  66. 66.
    PD-L1 IHC 22C3 pharmDx Interpretation manual: non-small cell lung cancer. https://www.agilent.com/cs/library/usermanuals/public/29158_pd-l1-ihc-22C3-pharmdx-nsclc-interpretation-manual.pdf. Accessed June 28 2018
  67. 67.
    VENTANA PD-L1 (SP142) Assay Interpretation guide for non-small cell lung cancer. http://passthrough.fw-notify.net/download/214026/http//productlibrary.ventana.com/ventana_portal/OpenOverlayServlet?launchIndex=1&objectId=740-48591015243US:. Accessed June 28 2018
  68. 68.
    PD-L1 IHC 22C3 pharmDx Interpretation manual: gastric or gastroesophageal junction adenocarcinoma. https://www.agilent.com/cs/library/usermanuals/public/29219_pd-l1-ihc-22C3-pharmdx-gastric-interpretation-manual_us.pdf. Accessed June 28 2018
  69. 69.
    VENTANA PD-L1 (SP263) Assay staining in urothelial carcinoma: interpretation guide. http://passthrough.fw-notify.net/download/681883/http://productlibrary.ventana.com/ventana_portal/OpenOverlayServlet?launchIndex=1&objectId=740-49071014738US. Accessed June 28 2018

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of PathologyUniversity Hospital BaselBaselSwitzerland

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