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H. Uruga
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-085 - Programmed Cell Death Ligand 1 (PD-L1) Expression in Stage II and III Lung Adenocarcinomas (ID 4663)
14:30 - 14:30 | Author(s): H. Uruga
- Abstract
Background:
Programmed cell death ligand 1 (PD-L1) expression could be used as a predictive marker for anti PD-1/PD-L1 therapy, especially for adenocarcinomas. However, the correlation between PD-L1 expression and the epidermal growth factor receptor (EGFR) mutational status has not been adequately studied. Additionally, whether PD-L1 positive expression is a prognostic factor or not is still debatable. We aimed to compare the clinicopathological findings including EGFR mutation and prognosis of stage II and III adenocarcinomas with positive or negative PD-L1 expression.
Methods:
Sixty-eight surgically resected stage II and III adenocarcinomas were included in this study. PD-L1 (clone SP142) expression was quantitatively assessed and considered to be positive when membranous staining of the tumor cells was >5%. Various clinicopathological parameters including pathologic findings were examined.
Results:
PD-L1 expression was positive in 11 of 68 (16.2%) adenocarcinomas. In the univariate analysis, PD-L1 positive expression was associated with abundant CD8+ lymphocytes (p<0.01), negative or unknown EGFR mutation (p=0.04), a predominant pathological pattern for adenocarcinoma based on the WHO 2015 classification (p=0.03), extracellular mucin production (p=0.05), and the presence of necrosis (p=0.01). Multivariate analysis showed that abundant CD8+ lymphocytes (p<0.01), a low N stage (p=0.05), and the presence of necrosis (p=0.054) were associated with PD-L1 positive expression. It also showed that PD-L1 positive expression was associated with longer RFS (p= 0.07, hazard ratio 6.21, 96% confidence interval 1.67-23.26). Abundant CD8+ lymphocytes and stage III adenocarcinoma were unfavorable factors for RFS. Figure 1
Conclusion:
According to the multivariate analysis, PD-L1 positive expression was associated with abundant CD8+ lymphocytes, a low N stage, and the presence of necrosis. Negative or unknown EGFR mutation was associated with PD-L1 positive expression according to the univariate analysis, but this association was not significant in the multivariate analysis. Regarding RFS, PD-L1 positive expression was a favorable prognostic factor independent of the surgical stage in the multivariate analysis.
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P3.01 - Poster Session with Presenters Present (ID 469)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.01-018 - Reproducibility in Classification of Small Lung Adenocarcinomas: An International Interobserver Study (ID 5222)
14:30 - 14:30 | Author(s): H. Uruga
- Abstract
Background:
The 2015 WHO classification for lung adenocarcinoma (ACA) provides criteria for diagnosis of adenocarcinoma in-situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (INV). Differentiating these entities can be difficult, and as understanding of prognostic significance increases, inconsistent classification is problematic.
Methods:
Sixty cases of lung ACAs (<2cm) were reviewed by an international panel of 6 lung pathologists. One slide reflecting overall morphology of each case was digitally scanned to an internet browser-based viewer. In round one, the panel independently reviewed each case to assess predominant pattern, invasive component size, and final diagnosis (AIS, MIA or INV). After a consensus conference among participants, a second round of independent review of the cases was performed. Additionally, a discussion on interpretation of elastic stain for evaluation of invasion will precede a third round of review with assessment of a concomitant elastic stain for each case. Statistical analysis was performed for each round.
Results:
In round one, the overall kappa value for AIS versus MIA and INV was 0.34 (fair agreement), and that for AIS and MIA versus INV was 0.44 (moderate agreement). The raters had 100% agreement on final diagnosis in 10 cases (AIS, n=2; MIA, n=2; INV, n=6). In 28 cases with poor agreement on final diagnosis and invasive measurement, inconsistent measurement of multifocal invasion led to wide variance in 5 cases, and subjectivity in pattern recognition led to variance in 23 cases. Misinterpretation of the WHO criteria for MIA resulted in 18 instances of misclassification across all raters. A case with a predominant mucinous lepidic pattern had a range of diagnoses (AIS, n=1; MIA, n=1; INV, n=4). In round two, the overall kappa value for AIS versus MIA and INV is 0.40 (fair agreement), and that for AIS and MIA versus INV is 0.36 (moderate agreement). The raters had 100% agreement on final diagnosis in 12 cases (AIS, n=3; MIA n=4; INV, n=5). Misinterpretation of the WHO criteria for MIA was seen in 6 instances. The intraobserver kappa coefficient ranged widely from 0.259 to 0.859.
Conclusion:
Interobserver agreement on diagnosis of small lung ACAs between raters was fair to moderate, with minimal improvement after a consensus conference. Inconsistent measurement of multifocal invasion, subjectivity in pattern recognition, misinterpretation of the WHO criteria, and subjective interpretation of mucinous ACA have contributed to interobserver discordance. A third round of evaluation is currently ongoing to assess for improvement and the utility of elastic stains.
