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Marie-Christine Copin
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P2.09 - Pathology (ID 174)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.09-17 - Real-World Concordance Across Pathologists for PD-L1 Scoring in Non-Small Cell Lung Cancer: Results from a Large Nationwide Initiative (ID 898)
10:15 - 18:15 | Author(s): Marie-Christine Copin
- Abstract
Background
PD-L1 immunohistochemistry (IHC) is an important routine biomarker in patients with metastatic and locally advanced non resectable non-small cell lung cancer (NSCLC). Currently, the thresholds of ≥1% and ≥50% of tumor cells stained are clinically relevant. Scoring concordance across pathologists was reported only in small groups of pathologists or across thoracic pathology experts. Here, we provide real-world concordance data in a large group of pathologists (n=161) with various experience of PD-L1 testing and practice in thoracic pathology.
Method
Twenty-nine NSCLC samples, mostly biopsies, stained in routine clinical pathology practice with PD-L1 IHC standardized assays (22C3, 28-8 and SP263), were selected to represent various PD-L1 expression levels. Slides were digitalized and scored for the percentage of tumor cells with membranous staining by 161 pathologists using an online digital platform. A consensus score was defined for each case by a group 15 expert pathologists. Data regarding experience, training and practice of PD-L1 testing were also collected for each pathologist.
Result
Consensus score determined by the expert group highly correlated with the median of scores for each case (correlation coefficient=0.992). Overall concordance across pathologists was moderate, higher for the ≥50% cutoff (K=0.64) than the ≥1% cutoff (K=0.58). A higher concordance was achieved in the expert group (15 pathologists) as compared to the other pathologists (146 pathologists), in particular for the ≥1% cutoff. Concordance across pathologists correlated with training to PD-L1 scoring as well as the number of PD-L1 tests evaluated weekly. No correlation was found with the number of years of thoracic pathology practice or the type of pathology practice (private laboratory, community hospital, university hospital). The issues observed in the most discrepant cases were evaluated and described.
Conclusion
Concordance across pathologists for PD-L1 scoring in NSCLC was higher in the expert group of pathologists as compared to other pathologists, in particular for the ≥1% cutoff. Training to PD-L1 scoring and experience in routine pathology practice correlated with higher concordance. These data emphasize the importance of training to achieve a high concordance across pathologists in the real-world setting.
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-53 - High MET Overexpression Does Not Predict the Presence of MET Exon 14 Splice Mutations in NSCLC: Results from the IFCT Predict.amm Study (ID 2324)
10:15 - 18:15 | Author(s): Marie-Christine Copin
- Abstract
Background
MET exon 14 splice site (METex14) mutations were recently described in Non Small Cell Lung Cancer (NSCLC) and reported to correlate with efficacy of MET tyrosine kinase inhibitors. High diversity of these alterations make them hard to detect by DNA sequencing in clinical practice. Because METex14 mutations induce increased stabilization of the MET receptor, it is anticipated that these mutations are associated with MET overexpression. We aim to determine whether NSCLC with high MET overexpression could define a subset of patients with a high rate of METex14 mutations.
Method
From the IFCT Predict.amm cohort of 843 consecutive patients with a treatment-naïve advanced NSCLC who were eligible for a first-line therapy, 108 NSCLC samples with high MET overexpression defined by an immunochemistry (IHC) score 3+ were tested for METex14 mutations using fragment length analysis combined with optimized targeted next generation sequencing (NGS). MET copy number analysis was also derived from the sequencing data.
Result
METex14 mutations were detected in two patients (2.2%) who also displayed a TP53 mutation and a PIK3CA mutation, respectively. A MET gene copy number increase was observed in 7 additional patients (7.7%). NGS analysis revealed inactivating mutations in TP53 (52.7%) and PTEN (1.1%) and oncogenic mutations in KRAS (28.6%), EGFR (7.7%), PIK3CA (4.4%), BRAF (4.4%), NRAS (2.2%), GNAS (1.1%) and IDH1 (1.1%).
Conclusion
The rate of METex14 mutations in NSCLC with high MET overexpression was similar to that found in unselected NSCLC. Moreover, we observed a high frequency of driver alterations in other oncogenes. Consequently these findings do not support the use of MET IHC as a surrogate marker for METex14 mutations.
