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Z. Wang
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-002 - Is T790M Mutation A "Regulator" for EGFR Signal Pathway Not an Oncogene? (ID 3786)
14:30 - 15:45 | Author(s): Z. Wang
- Abstract
Background:
Threonine 790 is regarded as a “gatekeeper” to inhibit ATP from binding to EGFR Tyrosine kinase domain. T790M mutation could increase the affinity for ATP. About 30% de novo T790M mutation was detected in NSCLC patients and showed spatiotemporal heterogeneity and variation in individual NSCLC patients. We hypothesize that T790M mutation may be a “regulating” mechanism for EGFR signal transduction pathway and is probably cleared quickly by DNA repair system in healthy persons.
Methods:
Peripheral blood samples were taken from 50 healthy volunteers, 12 resectable lung adenocarcinoma (LADC), 100 advanced LADC (11/100 acquired resistance for gefitinib). A novel cSMART assay (circulating single-molecule amplification and resequencing technology, which counts single allelic molecules in plasma base on next generation sequencing) was performed for detection and quantitation of EGFR mutation in ctDNA from plasma. Matching tumor biopsy samples were obtained from 100 advanced LADC, the EGFR gene mutations were determined by amplification refractory mutation system (ARMS) -PCR analysis.
Results:
The sensitivity and specificity of cSMART plasma assay for EGFR L858R, 19del and T790M was showed in Table 1. The sensitivity and specificity for T790M was obviously lower (50.0% and 72.9% respectively). No L858R and 19del but 14.0% T790M DNA copies were found in plasma from 50 healthy volunteers, and only 1 copy T790M was detected. The T790M positive rate of resectable and advanced LADC patients were almost similar (33.3% and 28.0%) in plasma, 1 or 2 T790M copies were found in the resectable patients and varied from 1 to 622 T790M copies with an average of 34.0 in advanced LADC patients. Patients with acquired resistance to gefitinib, 45.4% harbored T790M with an average of 268.2 copies in plasma. All but one advanced patients harboring T790M mutation were accompanied with other EGFR mutations.
Conclusion:
T790M mutation may be of a “regulator” and has physiological function.Table 1 EGFR mutations detection by plasma cSMART assay and tumor samples ARMS-PCR in advanced LADC patients
EGFR mutations Sensitivity Specificity L858R 91.7%(22/24) 100.0%(76/76) 19Del 79.2%(19/24) 100.0%(76/76) T790M 50.0%(2/4) 72.9%(70/96)
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P1.02-003 - ROS1 (D4D6) is Reliable for Immunohisochemistry Detecting of ROS1 Fusion Lung Adenocarcinoma in Malignant Pleural Effusion (ID 3841)
14:30 - 15:45 | Author(s): Z. Wang
- Abstract
Background:
ROS1 fusion is of a low frequency genetic alteration in non-small cell lung cancer (NSCLC). The clinical trial showed that NSCLC patients harboring ROS1 fusion could benefit from crizotinib treatment. Several studies reported that immunohistochemistry (IHC) could be employed as a screening method for detecting ROS1 fusion in tumor tissue using Anti-ROS1(D4D6) antibody. Malignant pleural effusion (MPE) is the common sample type in advanced NSCLC, the reliability of ROS1(D4D6) for detecting ROS1 fusion in MPE cell blocks (CBs) should be explored.
Methods:
Anti-ROS1(D4D6) monoclonal antibody (Cell Signaling Technology, Danvers, USA) IHC testing was performed on 227 formalin fixed paraffin embedded (FFPE) MPE CBs from lung adenocarcinoma patients. RT-PCR using ROS1 fusion gene detection kit (AmoyDx) was performed to detected ROS1 gene fusion as a comfirming test. Some other lung cancer driver genes were also detected in both IHC/RT-PCR ROS1 positive samples, among which EGFR, KRAS, BRAF, PIK3CA and HER2 20 exon mutation was tested by amplification refractory mutation system kits(AmoyDx), ALK and RET fusion was tested by RT-PCR kits(AmoyDx).
Results:
4 of 227 MPE samples(1.76%) of lung adenocarcinoma were interpreted as ROS1 fusion-positive cases by IHC staining, and the cytoplasmic and membranous granular positive signals were displayed. Comparison with RT-PCR testing results, 3 of 4 IHC positive cases were verified by RT-PCR, the sensitivity was 100% and specificity of was 99.6%. The clinicopathologic features and other genes status of 3 both IHC/RT-PCR positive patients were showed Table 1. One ROS1 IHC/RT-PCR positive lung adenocarcinoma patient received crizotinib therapy and obtained partial response.
Conclusion:
ROS1 (D4D6) would be a reliable antibody for screening ROS1 fusion-positive lung adenocarcinoma on FFPE MPE CBs by IHC assay and shows high specificity in the FFPE MPE CBs samples .Table 1 Clinicopathologic features and genes status of ROS1 IHC/RT-PCR positive patients
E/K/B/P/H: EGFR/KRAS/BRAF/PIK3CA/HER-2 20 exon mutation, A/R: ALK/RET fusion, WT: wild type, PEM+CIS: Pemetrexed plus Cisplatin,PR: partial response, m: monthsGender Age Smoking TTF1/ P63 E/k/B/ P/H A/R Therapy Efficacy PFS/Follow -up p1 Male 55 Smoker +/- WT WT crizotinib PR 10m+/alive p2 Female 60 Never +/- WT WT No 1m/Dead P3 Male 62 Never +/- WT WT PEM+CIS PR 9m+/alive
