A Harmonization Study for the Use of 22C3 PD-L1 Immunohistochemical Staining on Ventana's Platform.
Immunotherapy is a novel treatment for lung cancer. Pembrolizumab (Merck Sharp and Dohme, Kenilworth, NJ) is a monoclonal antibody against programmed cell death 1 that has been approved for use with NSCLC together with a companion diagnostic by Dako (Carpinteria, CA). Ventana's BenchMark XT (Ventana Medical Systems, Tucson, AZ) is a widely used immunohistochemical (IHC) platform. However, data on its reliability and reproducibility with the 22C3 antibody are scant.



We performed a comprehensive calibration of 22C3 programmed cell death ligand 1 (PD-L1) staining on the BenchMark XT platform using Dako's prediluted 22C3 anti-PD-L1 primary antibody with two of Ventana's detection systems. Forty-one random cases of NSCLC were then independently evaluated by two pathologists. Each case was scored using Dako- or Ventana-stained slides. The scores obtained with the two 22C3 Ventana assays were compared with those obtained using the Dako 22C3 IHC platform.



The Dako IHC platform stratified eight, seven, and 26 cases as being strongly positive, weakly positive, and negative for PD-L1, respectively, whereas 36 of 41 cases (87.8%) had the same results with Ventana's UltraView 22C3 protocol (Pearson's correlation score 0.91, p < 0.0001). Moreover, 35 of 41 cases (85.3%) had the same results with Ventana's OptiView 22C3 protocol (Pearson's correlation score 0.89, p < 0.0001).



The results of this study demonstrate that the same PD-L1 IHC algorithm can be reliably applied to Ventana's BenchMark XT platform. Furthermore, we were able to detect all of the strongly positive cases with high interobserver and intraobserver agreement by using the Ventana platform. These findings suggest that the Ventana platform can be used to stratify patients for pembrolizumab-based immunotherapy.
Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Tzahi
T
Neuman
Gamidor Diagnostics Inc., Petah Tikva, Israel.
Michal
M
London
Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Juliane
J
Kania-Almog
Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Anna
A
Litvin
Rambam Medical Center, Haifa, Israel.
Yaniv
Y
Zohar
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Rabin Medical Center, Petah Tikva, Israel.
Ludmila
L
Fridel
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Assaf-Ha'rofe Medical Center, Tzrifin, Israel.
Judith
J
Sandbank
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Sheba Medical Center, Ramat Gan, Israel.
Iris
I
Barshak
Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: giladwv@tlvmc.gov.il.
Gilad W
GW
Vainer
D061067:Antibodies, Monoclonal, Humanized / Q000032:analysis / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000276:immunology; D015203:Reproducibility of Results; D013194:Staining and Labeling / Q000379:methods
D061067:Antibodies, Monoclonal, Humanized; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C582435:pembrolizumab
Dako; Harmonization; IHC; PD-L1; Ventana