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Teh-Ying Chou
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-066 - PDL-1 Expression of Tumor Cell, Macrophage, and Immune Cells on Pleural Effusion (ID 9841)
09:30 - 09:30 | Author(s): Teh-Ying Chou
- Abstract
Background:
Immune checkpoint inhibitors provide a new treatment strategy for lung cancer. Therefore, microenvironment of tumor and interaction between immune cells and tumor cells become more important. Until now, the most frequently used marker to predict treatment response is immunohistochemical (IHC) stain of tumor PD-L1. However, the microenvironment of malignant pleural effusion is not clear. Weather we could use IHC stain of PD-L1 on cells of pleural effusion to predict treatment response have not been studied, either.
Method:
We retrospective enrolled patients who received malignant pleural effusion drainage and had cell blocks specimens from 2014-2016. IHC stain for PD-L1 was performed for tumor cells, immune cells, and macrophage of all cell block specimens. An experienced pathologist reviewed all the cell block cytology. The intensity of IHC stain was graded into grade 0, 1, 2, and 3. We also collected the clinicopathological characteristics of all patients.
Result:
PD-L1 expression of pleural effusion tumor cells was associated with the PD-L1 expression of pleural effusion macrophage (p=0.003) and immune cells (p<0.001). However, PD-L1 expression of immune cells is not associated with that of macrophages. PD-L1 expression of tumor cells is correlated with gender (p=0.012), smoking status (p=0.032), and ECOG performance status (p=0.017). Finally, PD-L1 expression of immune cells was associated with overall survival of our patients (p=0.004).
Conclusion:
These results suggested that there might be an immune interaction of pleural effusion tumor cells with macrophage/immune cells, and low expression of PDL1 expression of immune cell are associated with poor survival of lung cancer patients with malignant pleural effusion.
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P1.02 - Biology/Pathology (ID 614)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.02-008 - Expression of Mismatch Repair Proteins Associates with Survival and Response to EGFR Tyrosine Kinase Inhibitors in Lung Adenocarcinoma Patients (ID 9167)
09:30 - 09:30 | Author(s): Teh-Ying Chou
- Abstract
Background:
Mismatch repair (MMR) pathway is a fundamental cellular process required for the maintenance of genomic stability. Recently, a growing body of evidence suggests that a non-canonical MMR (ncMMR) function may be present as a source of mutations in human cells, which could lead to tumorigenesis. The dual functions of MMR with anti-mutagenic and mutagenic activities complicate its role in disease. Given that the functional role of MMR in lung cancer was rarely reported and is still controversial, the current study aimed to address the clinical significance of MMR proteins and their associations with therapeutic biomarkers in lung adenocarcinoma.
Method:
A panel of tissue microarrays containing 442 lung adenocarcinomas was examined for the expression of MMR proteins MLH1, PMS2, MSH2 and MSH6 using immunohistochemistry. The associations between MMR expression and clinicopathological features, patients’ survival as well as therapeutic biomarkers including EGFR mutation and PD-L1 expression were analyzed.
Result:
MLH1, PMS2, MSH2 and MSH6 protein expression significantly correlated with one another in lung adenocarcinoma (p<0.001). Neither age nor sex nor predominant histological pattern correlated with their expression, except that only MSH2 expression positively associated with the solid-pattern growth (p<0.05). Survival analyses showed that high expression of each MMR protein statistically correlated with poor patients’ overall and progression-free survivals (p<0.05). For therapeutic biomarker analysis, expression of MMR or PD-L1 independently associated with poor patients’ overall survival, but no significant correlation between their expression was observed. High expression of MLH1, MSH2 and MSH6 (p<0.05) but not PMS2 (p=0.12) was linked to poor survival in EGFR mutation-positive patients. To examine EGFR-TKI treatment response, the outcomes of 50 patients with EGFR mutation-positive tumors treated with EGFR-TKI were included for further analysis. Interestingly, patients with high expression of MLH1 in tumors showed a worse progression-free survival after EGFR-TKI treatment (n = 23, 13.8 months, 95% CI: 6.5 to 21.1 months) than those with low expression (n =27, 25.6 months, 95% CI: 10.9 to 40.3 months).
Conclusion:
MMR proteins are overexpressed in lung adenocarcinoma and significantly associate with poor patients’ survival, which may have a prognostic value in predicting patients’ drug response and clinical outcomes. Our results also raise a possibility that ncMMR function may participate in the tumorigenesis of lung adenocarcinoma.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-044 - Diagnosis and Monitoring of EGFR Mutation Status with cfDNA in Advanced NSCLC: A Prospective Single Institution Study in Asia (ID 9445)
09:30 - 09:30 | Presenting Author(s): Teh-Ying Chou
- Abstract
Background:
NSCLC patients in advanced stage with tumors that harbor EGFR sensitizing mutations are eligible for treatment with tyrosine kinase inhibitors (TKI) due to a high likelihood of response. The challenge with NSCLC is that often only small biopsy samples are available and when they are insufficient for molecular diagnostics, a repeat biopsy is not always possible and this results in delays in starting treatment. Molecular testing on circulating cell free DNA (cfDNA) from plasma is an alternative methodology that is readily applicable. We used the Roche cobas® EGFR Mutation Test V2 to diagnose (on tissue) and follow patients with EGFR sensitizing mutations to evaluate longitudinal changes in EGFR mutation status and SQI (Semi-quantitative Index) in plasma relative to standard of care for patients during TKI treatment. The sequential EGFR SQI values will be used to evaluate the relationship between molecular and clinical responses.
Method:
We included 60 patients (36 F/24 M) who had at least three follow up blood samples drawn post TKI treatment start. Ten ml of blood was collected in EDTA tubes from each subject at every visit. All patients had both tissue as well as baseline plasma EGFR results available. Serial follow up plasma samples were available on all patients. All subjects were treatment naïve, 80% (48/60) had no history of smoking and majority (45/60, 75%) presented with extra thoracic disease with clinical stages ranging between III-IV at diagnosis.
Result:
The L858R mutation was the most common EGFR mutation detected (58.3%) on the tissue followed by exon 19 deletion (35.0%). Two patients had dual mutations detected on tissue as well as in the baseline plasma. Plasma cfDNA analysis detected EGFR mutations in 78% of the baseline samples. Analysis of the serial plasma collected from patients who progressed while on 1[st] line TKI showed reappearance of the original EGFR sensitizing mutations with increasing SQI levels before emergence of a T790M mutation. T790M mutation was detected in 20.0% (12/60) of the patients on TKI treatment.
Conclusion:
This study clearly demonstrates that EGFR mutations can be reliably detected in plasma of NSCLC patients to confidently diagnose the presence of TKI resistance mutations using the Roche cobas® EGFR Mutation Test V2. Additionally, plasma SQI measurement can be used to monitor patients to detect the development of molecular TKI resistance. We will also show that serial measurement in the EGFR SQI can predict the relationship between molecular and clinical responses as well as tumor progression.
