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Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients
Published on: September 25, 2018
Correlation between PD-L1 expression (clones 28-8 and SP263) and histopathology in lung adenocarcinoma
Alejandro García1, Gonzalo Recondo2, Martín Greco2
1Department of Pathology, Center for Medical Education and Clinical Research (CEMIC), Argentina.
Abstract:
Lung cancer is the leading cause of cancer-related death worldwide. Recent advances in the management of non-small cell carcinoma are focused on the discovery of targeted therapies and novel immunotherapy strategies for patients with advanced disease. Treatment with anti PD-(L)1 immune checkpoint inhibitors requires the development of predictive biomarkers to select those patients that can most benefit from these therapies. Several immunohistochemical biomarkers have been developed in different technological platforms. However, the most useful and accessible for the daily clinical practice need to be selected. The objective of this study was to compare PD-L1 expression by automated immunohistochemistry in lung adenocarcinoma (ADC) FFPE samples with clones 28-8 and SP263 performed with the BenchMark GX automated staining instrument. To further determine interobserver agreement between two pathologists, and to correlate the results with histologic and pathology variables. FFPE tissue from 40 samples obtained from patients with lung ADC were reviewed retrospectively. Among all studied specimens, 53% of samples presented <1% of positive tumor cells with the 28-8 clone and 50% had <1% of PD-L1 expression in tumor cells with the SP263 clone; PD-L1 expression between ≥1 and <5% was observed in 18% and 24%; ≥5 and <50% PD-L1 expression in 18% and 21%; and ≥50% PD-L1 expression in 11% and 5% of samples, respectively. Similar results between antibodies were observed in 84% of cases for each of the four PD-L1 cutoff groups (Pearson's score 0.90, p < 0.00001). The interobserver degree of agreement calculated with Kappa was 0.75 (95%CI: 0.57-0.93), z = 7.08; p < 0.001. Lepidic, acinar and mucinous patterns had predominantly <1% PD-L1 expression, and the solid pattern subtype had high levels of PD-L1 staining using both clones. PD-L1 expression in less than 1% of tumor cells was similar in stages I/II compared to III/IV. No significant differences were observed in PD-L1 staining and quantification pattern between IHC antibodies 28-8 and SP263.
Insights
This study compared two PD-L1 immunohistochemistry clones (28-8 and SP263) in lung adenocarcinoma, finding similar expression patterns and high interobserver agreement. These results support their clinical utility for guiding immunotherapy. Keywords: PD-L1, lung adenocarcinoma, immunotherapy, biomarkers.
Area of Science:
- Oncology
- Immunotherapy
- Pathology
Background:
- Lung cancer remains a leading cause of cancer mortality globally.
- Anti PD-(L)1 immune checkpoint inhibitors offer novel treatment strategies for advanced non-small cell lung cancer.
- Predictive biomarkers, such as PD-L1 expression, are crucial for patient selection in immunotherapy.
Purpose of the Study:
- To compare the performance of two automated immunohistochemistry (IHC) clones (28-8 and SP263) for PD-L1 expression analysis in lung adenocarcinoma (ADC) FFPE samples.
- To assess interobserver agreement between pathologists in PD-L1 scoring.
- To correlate PD-L1 expression with histological and pathological variables in ADC.
Main Methods:
- Retrospective analysis of 40 lung ADC FFPE tissue samples.
- Automated IHC staining using BenchMark GX instrument with PD-L1 clones 28-8 and SP263.
- Quantitative assessment of PD-L1 tumor cell expression and interobserver agreement analysis (Kappa statistic).
Main Results:
- Both 28-8 and SP263 clones demonstrated similar PD-L1 expression patterns across various cutoffs, with 84% concordance.
- High interobserver agreement was observed (Kappa = 0.75), indicating reliable scoring.
- Solid tumor pattern showed higher PD-L1 expression compared to lepidic, acinar, and mucinous patterns; no significant difference in early vs. late stages.
Conclusions:
- Automated IHC using both PD-L1 clones 28-8 and SP263 provides comparable and reproducible results in lung ADC.
- The high interobserver agreement supports the clinical utility of these assays for guiding immunotherapy decisions.
- Histological subtype (solid pattern) is associated with higher PD-L1 expression, suggesting potential value in routine pathology.

