Discordance of PD-L1 Expression at the Protein and RNA Levels in Early Breast Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Cohorts
2.2. Tissue Microarrays (TMA), IHC Methods and Scoring of Commercially Available Antibodies
2.3. Cell Lines and FFPE Cell Blocks
2.4. Immunofluorescence
2.5. RNA In Situ Hybridization Combined with Immunofluorescence
2.6. Multiplex Fluorescent Immunohistochemistry
2.7. Gene Expression Analysis
2.8. Statistical Analysis
3. Results
3.1. Patient Cohorts, Characteristics, and Tissue Availability
3.2. Feasibility and Analytical Validity of PD-L1 mRNA, Protein and Simultaneous Detection in Breast Cancer Cell Lines
3.3. PD-L1 Protein Expression with SP142 and SP263 IHC Antibodies
3.4. Positivity Rates of PD-L1 Protein and mRNA Expression in BC Tissue
3.4.1. Positivity Rate of PD-L1 IF Expression
3.4.2. Positivity Rate of PD-L1 RNAscope® Expression
3.5. Concordance of PD-L1 Protein and mRNA Levels
3.6. PD-L1 Protein and mRNA Heterogeneity
3.6.1. Protein Heterogeneity
3.6.2. mRNA Heterogeneity
3.7. PD-L1 Expression in Different Cell Populations and Cellular Compartments
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Methodology | SP142 n (%) | SP263 n (%) | IF n (%) | RNAscope n (%) | MFI n (%) | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
+/+ | −/− | Concordant | p-Value * | +/+ | −/− | Concordant | p-Value * | +/+ | −/− | Concordant | p-Value * | +/+ | −/− | Concordant | p-Value * | +/+ | −/− | Concordant | p-Value * | |
SP142 | 21 (16.4) | 107 (83.6) | - | - | 14 (12.3) | 84 (74.3) | 108 (86.6) | <0.001 | 18 (17.0) | 24 (22.6) | 42 (49.6) | 0.038 | 10 (9.4) | 53 (50.0) | 63 (59.4) | 0.277 | 12 (11.4) | 53 (50.5) | 65 (61.9) | 0.032 |
SP263 | 14 (12.3) | 84 (74.3) | 108 (86.6) | <0.001 | 23 (19.5) | 95 (70.9) | - | - | 18 (18.5) | 18 (18.5) | 36 (37) | 0.355 | 10 (10.3) | 43 (44.3) | 53 (54.6) | 0.732 | 12 (12.2) | 49 (50.0) | 61 (62.2) | 0.046 |
IF | 18 (17.0) | 24 (22.6) | 42 (49.6) | 0.038 | 18 (18.5) | 18 (18.5) | 36 (37) | 0.355 | 83 (76.1) | 26 (23.9) | - | - | 42 (38.5) | 22 (20.2) | 64 (58.7) | 0.002 | 35 (35.3) | 15 (15.1) | 50 (50.5) | 0.432 |
RNAscope | 10 (9.4) | 53 (50.0) | 63 (59.4) | 0.277 | 10 (10.3) | 43 (44.3) | 53 (54.6) | 0.732 | 42 (38.5) | 22 (20.2) | 64 (58.7) | 0.002 | 46 (42.2) | 63 (57.8) | - | - | 14 (14.1) | 27 (27.2) | 41 (41.4) | 0.056 |
MFI | 12 (11.4) | 53 (50.5) | 65 (61.9) | 0.032 | 12 (12.2) | 49 (50.0) | 61 (62.2) | 0.046 | 35 (35.3) | 15 (15.1) | 50 (50.5) | 0.432 | 14 (14.1) | 27 (27.2) | 41 (41.4) | 0.056 | 48 (44.4) | 60 (55.5) | - | - |
ACD Score | Cohort 1: Number of Areas Scored (%) | Cohort 2: Number of Areas Scored (%) |
---|---|---|
0 | 137 (62.8%) | 91 (81.3%) |
1 | 60 (27.5%) | 18 (16.1%) |
2 | 20 (9.2%) | 3 (2.7%) |
3 | 1 (0.5%) | 0 |
4 | 0 | 0 |
TOTAL | 218 (100%) | 112 (100%) |
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Zerdes, I.; Karafousia, V.; Mezheyeuski, A.; Stogiannitsi, M.; Kuiper, R.; Moreno Ruiz, P.; Rassidakis, G.; Bergh, J.; Hatschek, T.; Foukakis, T.; et al. Discordance of PD-L1 Expression at the Protein and RNA Levels in Early Breast Cancer. Cancers 2021, 13, 4655. https://doi.org/10.3390/cancers13184655
Zerdes I, Karafousia V, Mezheyeuski A, Stogiannitsi M, Kuiper R, Moreno Ruiz P, Rassidakis G, Bergh J, Hatschek T, Foukakis T, et al. Discordance of PD-L1 Expression at the Protein and RNA Levels in Early Breast Cancer. Cancers. 2021; 13(18):4655. https://doi.org/10.3390/cancers13184655
Chicago/Turabian StyleZerdes, Ioannis, Vaia Karafousia, Artur Mezheyeuski, Maria Stogiannitsi, Raoul Kuiper, Pablo Moreno Ruiz, George Rassidakis, Jonas Bergh, Thomas Hatschek, Theodoros Foukakis, and et al. 2021. "Discordance of PD-L1 Expression at the Protein and RNA Levels in Early Breast Cancer" Cancers 13, no. 18: 4655. https://doi.org/10.3390/cancers13184655
APA StyleZerdes, I., Karafousia, V., Mezheyeuski, A., Stogiannitsi, M., Kuiper, R., Moreno Ruiz, P., Rassidakis, G., Bergh, J., Hatschek, T., Foukakis, T., & Matikas, A. (2021). Discordance of PD-L1 Expression at the Protein and RNA Levels in Early Breast Cancer. Cancers, 13(18), 4655. https://doi.org/10.3390/cancers13184655