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S. Wu
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MA 12 - Circumventing EGFR Resistance (ID 665)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Wan Ling Tan, Nobuyuki Yamamoto
- Coordinates: 10/17/2017, 11:00 - 12:30, F205 + F206 (Annex Hall)
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MA 12.09 - EGFR T790M Co-Exist with Sensitive Mutation in the Same Cell Group in Lung Adenocarcinoma Patients (ID 9414)
12:00 - 12:05 | Author(s): S. Wu
- Abstract
- Presentation
Background:
EGFR TKI therapy has improved lung adenocarcinoma patients’ prognosis tremendously, but almost all of the patients inevitably develop acquired resistance, and EGFR T790M mutation is the major contributors. T790M restores the EGFR tyrosine kinase domain affinity to ATP, and therefore gefitinib is displaced from the binding pocket, and the ‘driving’ signal for proliferation is switched on again. Previous work has shown that after TKI therapy, lung adenocarcinoma patients kept the sensitive mutation and acquired resistance mutation simultaneously by sequencing methods or in vitro cell line experiments. Whether the two different type mutations are in the same cell group or in two different cell groups is unknown. None of them has observed what was happening in the tumor cells after TKI therapy.
Method:
RNA in situ hybridization methods was employed to examined EGFR T790M and L858R mutation in lung adenocarcinoma cancer tissues which was obtained before and after TKI therapy. EGFR expression was examined by immunohistochemistry. EGFR mutation were detected by ARMS PCR methods.
Result:
Twenty five patients were enrolled in this study which were divided into 3 groups. Group 1: 5 patients who had concurrent primary T790M and sensitive EGFR mutation. Group 2: 14 patients who acquired T790M mutation after receiving TKI therapy. Among them, 6 patients had biopsy tissues before and after TKI therapy. 8 patients only own tissues after TKI therapy. Group 3: 6 patients who had sensitive EGFR mutation and received TKI therapy, but re-biopsy tissues didn’t had EGFR T790M. We found that the results of RNA ISH and ARMS PCR methods was identical in the majority of the examined tissues. Only one repeated biopsy tissue didn’t identify EGFR T790M after TKI therapy by PCR in group 3, while the RNA ISH method detected T790M in this tissue which contain only 150 tumor cells. In the serial cut slides, we observed that T790M and L858R mutations were in the same cell group, not only in the primary resistance cases, but also in the acquired resistance cases. For the two cases which had tissues available after receiving third generation TKI therapy, we observed that T790M disappeared in the repeated biopsy specimen, leaving the sensitive mutation which existed from the beginning.
Conclusion:
In the primary and acquired resistance tissues, EGFR sensitive mutation and T790M co-exist in the same cell groups. EGFR sensitive mutation is a trunk and drive mutation, while T790M is a passenger mutation during the treatment process by TKI therapy.
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-033 - The Association of PD-L1 Expression with Clinical Characteristics and EGFR and ALK Status in Lung Adenocarcinoma (ID 8842)
09:30 - 09:30 | Author(s): S. Wu
- Abstract
Background:
Programmed cell death-1 (PD-1) inhibitor is one of important medicines of immunotherapy for cancers. Programmed cell death ligand-1 (PD-L1) expression is a valuable predictor for selection of patients by PD-1 inhibitors therapy. However, the correlation of PD-L1 expression with clinicopathologic features, EGFR and ALK status, and prognosis of lung adenocarcinoma remain controversial.
Method:
421 lung adenocarcinoma patients with identified EGFR and ALK status in tumor tissues were enrolled. Using tissue microarrays, PD-L1 expression was evaluated using clone SP263 antibody by immunohistochemistry (IHC) on Ventana Benchmark automated staining system. The association of PD-L1 expression with clinicopathologic characteristics, EGFR and ALK status and prognosis of lung adenocarcinoma were analysed.
Result:
A total of 404 patients were available for evaluation. The positve incidence of PD-L1 expression was 22.5% (91/404) (using a cutoff of ≥ 25%). Multivariate Logistic regression analysis showed PD-L1 expression was associated with advanced stage (ORR 2.190, 95% CI 1.313-3.651, P = 0.003), solid predominant subtype (ORR 3.594, 95% CI 1.826-7.073, P < 0.001), and wild-type epidermal growth factor receptor (EGFR) (ORR 1.895, 95% CI 1.091-3.291, P = 0.023), while it was not associated with ALK rearrangement. In multivariate analysis for OS by Cox hazard proportion model, patients with early stage (HR 2.495, 95% CI 2.003-3.106, P < 0.001) and EGFR mutations (HR 1.635, 95% CI 1.310-2.040, P < 0.001) had a significantly longer survival, while PD-L1 expression was not associated with OS of patients with lung adenocarcinoma (HR 0.847, 95% CI 0.655-1.094, P = 0.203).
Conclusion:
Positive PD-L1 expression in lung adenocarcinoma tissues was significantly associated with tumor advanced stage, solid predominant subtype, and wild-type EGFR, however, PD-L1 expression may not be a predictor of OS for patients with lung adenocarcinoma.
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P3.03 - Chemotherapy/Targeted Therapy (ID 719)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.03-004 - The Frequency and Clinical Implication of ALK, ROS1, RET and NTRK1 Gene Rearrangements in Adenosquamous Lung Carcinoma Patients (ID 8254)
09:30 - 09:30 | Author(s): S. Wu
- Abstract
Background:
Adenosquamous lung carcinoma (ASC) is a hybrid tumor made of adenocarcinoma and squamous cell carcinoma in one tumor. It is a rare disease with poorer prognosis comparing with the other common variants of non-small cell lung cancer (NSCLC). There is a persisting need for identifying more effective targeted therapy methods. Our previous study had examined the EGFR mutation status in lung ASC, the results showed that its mutation rate is similar with that of lung adenocarcinoma. Because the rarity of lung ASC, little is known about its gene rearrangement status and its relationship with the clinical characteristics.
Method:
ALK, ROS1, RET and NTRK1 gene rearrangement in lung ASC were examined by next generation sequencing methods, and further confirmed by fluorescent in situ hybridization (FISH) and/or immunohistochemistry methods. Tissue microarrays (TMAs) containing formalin fixed paraffin embedded (FFPE) lung ASC cases were used in this study.
Result:
This study included 53 cases of lung ASC totally. ALK/EML4 gene rearrangement was detected in 3 cases (5.7%), ROS1 fusion gene was detected in 1 cases (1.9%), RET gene rearrangement was detected in 1 case (1.9%). One of the ALK/EML4 rearrangement case had a concurrent EGFR exon 21 L858R mutation. All the rearrangement results can be further confirmed by FISH and/or immunohistochemistry methods. No association were identified between ALK/EML4 rearrangement and patient age, tumor size, clinical stage, positive pleural invasion, lymphovascular invasion, smoking status, lymph node metastasis, therapy methods, recurrence free survival (RFS) time or overall survival duration.
Conclusion:
The gene rearrangement rate of lung ASC is similar with that of lung adenocarcinoma, which further support our suggestion that lung ASC is a peculiar subtype of lung adenocarcinoma with a poorer prognosis than lung adenocarcinoma.
