https://doi.org/10.4081/ejh.2021.3185
PD-L1 expression with QR1 and E1L3N antibodies according to histological ovarian cancer subtype: A series of 232 cases
Submitted: 1 October 2020
Accepted: 10 February 2021
Published: 10 March 2021
Accepted: 10 February 2021
Abstract Views: 970
PDF: 513
HTML: 14
HTML: 14
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Therapeutic strategies for epithelial ovarian cancers are evolving with the advent of immunotherapy, such as PD-L1 inhibitors, with encouraging results. However, little data are available on PDL-1 expression in ovarian cancers. Thus, we set out to determine the PD-L1 expression according to histological subtype. We evaluated the expression of two PD-L1 clones – QR1 and E1L3N – with two scores, one based on the percentage of labeled tumor cells (tumor proportion score, TPS) and the other on labeled immune cells (combined proportion score, CPS) in a consecutive retrospective series of 232 ovarian cancers. PD-L1 expression was more frequent in high grade serous carcinoma (27.5% with E1L3N clone and 41.5% with QR1 clone), grade 3 endometrioid carcinoma (25% with E1L3N clone and 50% with QR1 clone), and clear-cell carcinomas (27.3% with E1L3N clone and 29.6% with QR1 clone) than other histological subtypes with CPS score. Using the CPS score, 17% of cases were labeled with E1L3N vs 28% with QR1. Using the TPS score, 14% of cases were positive to E1L3N vs 17% for QR1. For TPS and CPS, respectively, 77% and 78% of the QR1 cases were concordant with E1L3N for the thresholds of 1%. Overall and progression-free survival between PD-L1 positive and PD-L1 negative patients were not different across all histological types, and each subtype in particular for serous carcinomas expressing PD-L1. Expression of PD-L1 is relatively uncommon in epithelium ovarian tumors. When positive, usually <10% of tumor cells are labeled. QR1 clone and CPS appear the best tools to evaluate PD-L1 expression.
Coburn SB, Bray F, Sherman ME, Trabert B. International patterns and trends in ovarian cancer incidence, overall and by histologic subtype. Int J Cancer 2017;140:2451-60.
DOI: https://doi.org/10.1002/ijc.30676
Institut National du Cancer. [Les cancers en France l’essentiel des faits et chiffres en 2017].[Report in French]. Available from: https://www.e-cancer.fr/Professionnels-de-sante/Les-chiffres-du-cancer-en-France/Epidemiologie-des-cancers/Donnees-globales
Nasioudis D, Sisti G, Kanninen T, Holcomb K, Tommaso MD, Fambrini M, et al. Epidemiology and outcomes of squamous ovarian carcinoma; a population-based study. Gynecol Oncol 2016;141:128-33.
DOI: https://doi.org/10.1016/j.ygyno.2016.02.004
Sankaranarayanan R, Ferlay J. Worldwide burden of gynaecological cancer: the size of the problem. Best Pract Res Clin Obstet Gynaecol 2006;20:207-25.
DOI: https://doi.org/10.1016/j.bpobgyn.2005.10.007
Bell D, Berchuck A, Birrer M, Chien J, Cramer DW, Dao F, et al. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 2011;474:609-15.
DOI: https://doi.org/10.1038/nature10166
Ventriglia J, Paciolla I, Pisano C , Cecere SC, Napoli MD, Tambaroet R, et al. Immunotherapy in ovarian, endometrial and cervical cancer: State of the art and future perspectives. Cancer Treat Rev 2017;59:109-16.
DOI: https://doi.org/10.1016/j.ctrv.2017.07.008
Nair D, Rådestad E, Khalkar P, Diaz-Argelich N, Schröder A, Klynning C, et al. Methylseleninic acid sensitizes ovarian cancer cells to T-cell mediated killing by decreasing PDL1 and VEGF Levels. Front Oncol 2018;8:407.
DOI: https://doi.org/10.3389/fonc.2018.00407
Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002;8:793-800.
DOI: https://doi.org/10.1038/nm730
Dermani FK, Samadi P, Rahmani G, Kohlan AK, Najafi R. PD-1/PD-L1 immune checkpoint: Potential target for cancer therapy. J Cell Physiol 2019;234:1313-25.
DOI: https://doi.org/10.1002/jcp.27172
Wang Q, Lou W, Di W, Wu X. Prognostic value of tumor PD-L1 expression combined with CD8+ tumor infiltrating lymphocytes in high grade serous ovarian cancer. Int Immunopharmacol 2017;52:7-14.
DOI: https://doi.org/10.1016/j.intimp.2017.08.017
Buderath P, Mairinger F, Mairinger E, Böhm K, Mach P, Schmid KW, et al. Prognostic significance of PD-1 and PD-L1 positive tumor-infiltrating immune cells in ovarian carcinoma. Int J Gynecol Cancer 2019;29:1389-95.
DOI: https://doi.org/10.1136/ijgc-2019-000609
Pujade-Lauraine E, Fujiwara K, Dychter SS, Devgan G, Monk BJ. Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase III study design. Future Oncol 2018;14:2103-13.
DOI: https://doi.org/10.2217/fon-2018-0070
Varga A, Piha-Paul S, Ott PA, Mehnert JM, Berton-Rigaud D, Morosky A, et al. Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Gynecol Oncol 2019;152:243-50.
DOI: https://doi.org/10.1016/j.ygyno.2018.11.017
Hamanishi J, Mandai M, Ikeda T, Minami M, Kawaguchi A, Murayama T, et al. Safety and antitumor activity of anti-PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol 2015;33:4015-22.
DOI: https://doi.org/10.1200/JCO.2015.62.3397
Fan CA, Reader J, Roque DM. Review of immune therapies targeting ovarian cancer. Curr Treat Options Oncol 2018;19:74.
DOI: https://doi.org/10.1007/s11864-018-0584-3
Wang L. Prognostic effect of programmed death-ligand 1 (PD-L1) in ovarian cancer: a systematic review, meta-analysis and bioinformatics study. J Ovarian Res 2019;12:37.
DOI: https://doi.org/10.1186/s13048-019-0512-6
Piao J, Lim HJ, Lee M.Prognostic value of programmed cell death ligand-1 expression in ovarian cancer: an updated meta-analysis. Obstet Gynecol Sci 2020;63:346-56.
DOI: https://doi.org/10.5468/ogs.2020.63.3.346
Udall M, Rizzo M, Kenny J, Doherty J, Dahm SA, Robbins P, et al. PD-L1 diagnostic tests: a systematic literature review of scoring algorithms and test-validation metrics. Diagn Pathol 2018;13:12.
DOI: https://doi.org/10.1186/s13000-018-0689-9
Zhu J, Wen H, Bi R, Wu Y, Wu X. Prognostic value of programmed death-ligand 1 (PD-L1) expression in ovarian clear cell carcinoma. J Gynecol Oncol 2017;28:e77.
DOI: https://doi.org/10.3802/jgo.2017.28.e77
Huang LJ, Deng XF, Chang F, Wu XL, Wu Y, Diao QZ. Prognostic significance of programmed cell death ligand 1 expression in patients with ovarian carcinoma: A systematic review and meta-analysis. Medicine (Baltimore) 2018;97:e12858.
DOI: https://doi.org/10.1097/MD.0000000000012858
Viera AJ, Garrett JM. Understanding interobserver agreement: the kappa statistic. Fam Med 2005;37:360-3.
Schmoeckel E, Hofmann S, Fromberger D, Rottmann M, Luthardt B, Burges A, et al. Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma. Virchows Arch. 2019;474:599-608.
DOI: https://doi.org/10.1007/s00428-019-02528-6
Büttner R, Gosney JR, Skov BG, Adam J, Motoi N, Bloom KJ, et al. Programmed death-ligand 1 immunohistochemistry testing: A review of analytical assays and clinical implementation in non-small-cell lung cancer. J Clin Oncol 2017;35:3867-76.
DOI: https://doi.org/10.1200/JCO.2017.74.7642
Adam J, Le Stang N, Rouquette I, Cazes A, Badoual C, Pinot-Roussel H, et al. Multicenter harmonization study for PD-L1 IHC testing in non-small-cell lung cancer. Ann Oncol 2018;29:953-8.
DOI: https://doi.org/10.1093/annonc/mdy014
Qu QX, Xie F, Huang Q, Zhang XG. Membranous and cytoplasmic expression of PD-L1 in ovarian cancer cells. Cell Physiol Biochem 2017;43:1893-906.
DOI: https://doi.org/10.1159/000484109
Drakes ML, Mehrotra S, Aldulescu M, Potkul RK, Liu Y, Grisoli A, et al. Stratification of ovarian tumor pathology by expression of programmed cell death-1 (PD-1) and PD-ligand- 1 (PD-L1) in ovarian cancer J Ovarian Res 2018;11:43.
DOI: https://doi.org/10.1186/s13048-018-0414-z
Koh J, Go H, Keam B, Kim MY, Nam SJ, Kim TM, et al. Clinicopathologic analysis of programmed cell death-1 and programmed cell death-ligand 1 and 2 expressions in pulmonary adenocarcinoma: comparison with histology and driver oncogenic alteration status. Mod Pathol 2015;28:1154-66.
DOI: https://doi.org/10.1038/modpathol.2015.63
Tsao MS, Kerr MK, Dacic S, Yatabe Y, Hirsch FR. IASLC atlas of PD-L1 immunohistochemistry testing in lung cancer. International Association for the Study of Lung Cancer. 2019.
Brandone N, Mascaux C, Caselles K, Rouquette I, Lantuejoul S, Garcia S. Validation of the QR1 antibody for the evaluation of PD-L1 expression in non-small cell lung adenocarcinomas. Appl Immunohistochem Mol Morphol 2020;28:23-9.
DOI: https://doi.org/10.1097/PAI.0000000000000758
Cohen EEW, Bell RB, Bifulco CB, Burtness B, Gillison ML, Harrington KJ, et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). J Immunother Cancer 2019;7:184.
DOI: https://doi.org/10.1186/s40425-019-0662-5
Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 2018;379:2108-21.
DOI: https://doi.org/10.1056/NEJMoa1809615
Soderling JA, Reed MJ, Corsa A, Sage EH. Cloning and expression of murine SC1, a gene product homologous to SPARC. J Histochem Cytochem 1997;45823-35.
DOI: https://doi.org/10.1177/002215549704500607
Tumbarello DA, Andrews MR, Brenton JD. SPARC regulates transforming growth factor beta induced (TGFBI) extracellular matrix deposition and paclitaxel response in ovarian cancer cells. PLoS One 2016;11:e0162698.
DOI: https://doi.org/10.1371/journal.pone.0162698
John B, Naczki C, Patel C, Ghoneum A, Qasem S, Salih Z, Said N. Regulation of the bi-directional cross-talk between ovarian cancer cells and adipocytes by SPARC. Oncogene 2019;38:4366-83.
DOI: https://doi.org/10.1038/s41388-019-0728-3
Li M, Li H, Liu F, Bi R, Tu X, Chen L et al. Characterization of ovarian clear cell carcinoma using target drug-based molecular biomarkers: implications for personalized cancer therapy. J Ovarian Res 2017;10:9.
DOI: https://doi.org/10.1186/s13048-017-0304-9
Xiao X, Dong D, He W, Song L, Wang Q, Yue J, et al. Mismatch repair deficiency is associated with MSI phenotype, increased tumor-infiltrating lymphocytes and PD-L1 expression in immune cells in ovarian cancer. Gynecol Oncol 2018;149:146-54.
DOI: https://doi.org/10.1016/j.ygyno.2018.02.009
Zhu X, Zhao L, Lang J. The BRCA1 methylation and PD-l1 expression in sporadic ovarian cancer. Int J Gynecol Cancer 2018;28:1514-9.
DOI: https://doi.org/10.1097/IGC.0000000000001334
Strickland KC, Howitt BE, Shukla SA, Rodig S, Ritterhouse LL, Liu JF, et al. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. Oncotarget 2016;7:13587-98.
DOI: https://doi.org/10.18632/oncotarget.7277
Matulonis UA, Shapira-Frommer R, Santin AD, Lisyanskaya AS, Pignata S, Vergote I, et al. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: Results from the phase 2 KEYNOTE-100 study. Ann Oncol 2019;30:1080-7.
DOI: https://doi.org/10.1093/annonc/mdz135
Pawłowska A, Suszczyk D, Tarkowski R, Paduch R, Kotarski J, Wertel I. Programmed death-1 receptor (PD-1) as a potential prognosis biomarker for ovarian cancer patients. Cancer Manag Res 2020;12:9691-709.
DOI: https://doi.org/10.2147/CMAR.S263010
Kim KH, Choi KU, Kim A, Lee SJ, Lee JH, Suh DS, et al. PD-L1 expression on stromal tumor-infiltrating lymphocytes is a favorable prognostic factor in ovarian serous carcinoma. J Ovarian Res 2019;12:56.
DOI: https://doi.org/10.1186/s13048-019-0526-0
Xue C, Xu Y, Ye W, Xie Q, Gao H, Xu B, et al. Expression of PD-L1 in ovarian cancer and its synergistic antitumor effect with PARP inhibitor. Gynecol Oncol 2020;157:222-33.
DOI: https://doi.org/10.1016/j.ygyno.2019.12.012
Dirix LY, Takacs I, Jerusalem G, Nikolinakos P, Arkenau HT, Forero-Torres A, et al. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study. Breast Cancer Res Treat 2018;167:671-86.
DOI: https://doi.org/10.1007/s10549-017-4537-5
Mesnage SJL, Auguste A, Genestie C, Dunant A, Pain E, Drusch F, et al. Neoadjuvant chemotherapy (NACT) increases immune infiltration and programmed death-ligand 1 (PD-L1) expression in epithelial ovarian cancer (EOC). Ann Oncol 2017;28:651-7.
DOI: https://doi.org/10.1093/annonc/mdw625
Ethics Approval
The study was approved by the Ethics Committee “Comité d’éthique de la recherche en Obstétrique et Gynécologie (CEROG)” (number CEROG 2019-GYN-1102 “phenotypic profiles identified in epithelial ovarian cancers”)How to Cite
Eymerit-Morin, C., Ilenko, A., Gaillard, T., Varinot, J., Compérat, E., Bendifallah, S., & Darai, E. (2021). PD-L1 expression with QR1 and E1L3N antibodies according to histological ovarian cancer subtype: A series of 232 cases. European Journal of Histochemistry, 65(1). https://doi.org/10.4081/ejh.2021.3185
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- G. Chene, N. Radosevic-Robin, A.S. Tardieu, A. Cayre, I. Raoelfils, P. Dechelotte, J. Dauplat, F. Penault Llorca, Morphological and immunohistochemical study of ovarian and tubal dysplasia associated with tamoxifen , European Journal of Histochemistry: Vol. 58 No. 2 (2014)
- X.C. Xu, X. Abuduhadeer, W.B. Zhang, T. Li, H. Gao, Y.H. Wang, Knockdown of RAGE inhibits growth and invasion of gastric cancer cells , European Journal of Histochemistry: Vol. 57 No. 4 (2013)
- Xin Kong, Qi Wang, Jie Li, Ming Li, Fusheng Deng, Chuanying Li, Mammaglobin, GATA-binding protein 3 (GATA3), and epithelial growth factor receptor (EGFR) expression in different breast cancer subtypes and their clinical significance , European Journal of Histochemistry: Vol. 66 No. 2 (2022)
- Y. Zhang, W.Y. Ye, J.Q. Wang, S.J. Wang, P. Ji, G.Y. Zhou, G.P. Zhao, H.L. Ge, Y. Wang, dCTP pyrophosphohydrase exhibits nucleic accumulation in multiple carcinomas , European Journal of Histochemistry: Vol. 57 No. 3 (2013)
- Yiming Zhang, Wanqiong Zheng, Liang Zhang, Yechun Gu, Lihe Zhu, Yingpeng Huang, LncRNA FBXO18-AS promotes gastric cancer progression by TGF-β1/Smad signaling , European Journal of Histochemistry: Vol. 67 No. 2 (2023)
- Xiangjun Lu, Jian Shen, Siyuan Huang, Dongdong Liu, Haitao Wang, Tumor cells-derived exosomal PD-L1 promotes the growth and invasion of lung cancer cells in vitro via mediating macrophages M2 polarization , European Journal of Histochemistry: Vol. 67 No. 3 (2023)
- Ying Wang, Shifa Yuan, Jing Ma, Hong Liu, Lizhen Huang, Fengzhen Zhang, Substance P is overexpressed in cervical squamous cell carcinoma and promoted proliferation and invasion of cervical cancer cells in vitro , European Journal of Histochemistry: Vol. 67 No. 3 (2023)
- A.K. Lindström, D. Hellberg, Immunohistochemical LRIG3 expression in cervical intraepithelial neoplasia and invasive squamous cell cervical cancer: association with expression of tumor markers, hormones, high-risk HPV-infection, smoking and patient outcome , European Journal of Histochemistry: Vol. 58 No. 2 (2014)
- L. Bao, Q. Li, Y. Liu, B. Li, X. Sheng, Y. Han, Q. Weng, Immunolocalization of NGF and its receptors in ovarian surface epithelium of the wild ground squirrel during the breeding and nonbreeding seasons , European Journal of Histochemistry: Vol. 58 No. 2 (2014)
- Michael W.L. Quirino, Amanda P.B. Albuquerque, Maria F.D. de Souza, Antônio F. da Silva Filho, Mário R. Martins, Maira G. da Rocha Pitta, Michelly C. Pereira, Moacyr J.B. de Melo Rêgo, alpha2,3 sialic acid processing enzymes expression in gastric cancer tissues reveals that ST3Gal3 but not Neu3 are associated with Lauren's classification, angiolymphatic invasion and histological grade , European Journal of Histochemistry: Vol. 66 No. 4 (2022)
You may also start an advanced similarity search for this article.
Publication Facts
Metric
This article
Other articles
Peer reviewers
2
2.4
Reviewer profiles N/A
Author statements
Author statements
This article
Other articles
Data availability
N/A
16%
External funding
N/A
32%
Competing interests
N/A
11%
Metric
This journal
Other journals
Articles accepted
57%
33%
Days to publication
159
145
- Editor & editorial board
- profiles
- Academic society
- N/A
- Publisher
- PAGEPress Publications, Pavia, Italy
To learn about these publication facts, click 
PF is maintained by the Public Knowledge Project
