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Z. Xie
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MINI 08 - Prognostic/Predictive Biomarkers (ID 106)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:T.E. Stinchcombe, N. Pavlakis
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 4a-4f
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MINI08.06 - Prognostic Significance of FGFR1 Amplification in Patients with Lung Squamous Cell Carcinoma (ID 814)
17:20 - 17:25 | Author(s): Z. Xie
- Abstract
- Presentation
Background:
The Fibroblast Growth Factor Receptor(FGFR) pathway especially FGFR1 gene copy number gain have attracted continuous attention of researchers for several years. Whereas due to different test methods and distinguishing criteria whether FGFR1 amplification related to patients smoking status or prognosis is still controversial.
Methods:
We used fluorescence in situ hybridization (FISH) to detect the gene copy number in paraffin-embedded tissue sections from 200 cases of pulmonary squamous cell carcinoma patients who underwent surgery in Guangdong Lung Caner Institute(GLCL) from 2008 to 2013. All samples had been identified as primary squamous cell carcinoma by postoperative pathology and informed consent. A tumor is defined as FGFR1 amplification positive when FISH results meet one of the following criteria after reviewing at least 100 tumor cells: (1) FGFR1/CEP-8 ratio≥2; (2) mean number of FGFR1 signals≥6; or if (3) ≥10% tumor cell containing more than 15 FGFR1 signals or large clusters. Among them, sample accord with the 3rd standard was defined as focal amplification.
Results:
Figure 1 We used fluorescence in situ hybridization (FISH) to detect the gene copy number in paraffin-embedded tissue sections from 200 cases of pulmonary squamous cell carcinoma patients who underwent surgery in Guangdong Lung Caner Institute(GLCL) from 2008 to 2013. All samples had been identified as primary squamous cell carcinoma by postoperative pathology and informed consent. A tumor is defined as FGFR1 amplification positive when FISH results meet one of the following criteria after reviewing at least 100 tumor cells: (1) FGFR1/CEP-8 ratio≥2; (2) mean number of FGFR1 signals≥6; or if (3) ≥10% tumor cell containing more than 15 FGFR1 signals or large clusters. Among them, sample accord with the 3rd standard was defined as focal amplification.
Conclusion:
Our results suggested that FGFR1 focal amplification might be an independent risk factor for patients overall survival. Patients with FGFR1 amplification were more likely to disease recurrence. Clinical characteristic including smoking status were not found in association with FGFR1 amplification, suggesting patients with FGFR1 amplification might not be fully enriched through only clinical factors.
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ORAL 16 - Clinical Care of Lung Cancer and Advanced Biopsies (ID 115)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:J.W. Neal, Q. Zhou
- Coordinates: 9/08/2015, 10:45 - 12:15, Mile High Ballroom 2a-3b
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ORAL16.07 - Intratumor Heterogeneity of EGFR Activating Mutations Analyzed in Single Cancer Cells in Advanced NSCLC Patients (ID 2311)
11:50 - 12:01 | Author(s): Z. Xie
- Abstract
- Presentation
Background:
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) can achieve dramatic response in EGFR activating mutation positive lung cancer patients. However, the duration of treatment is quite different. Some patients experienced longer progression-free survival (PFS) of more than 1 year, whereas some had PFS of shorter than 6 months. Our previous study showed that the relative EGFR mutation abundance in tumor tissues could predict benefit from EGFR-TKIs treatment. However, it still remains controversial whether the intratumor heterogeneity of EGFR activating mutation exists. This study explored the intratumor heterogeneity of EGFR activating mutation at the level of single cancer cell.
Methods:
Single H1975 cells which harbor EGFR exon 21 L858R mutation were isolated by flow cytometry (FCM). The whole DNA extracted from a single cell was submitted to perform nested polymerase chain reaction (PCR) amplification of EGFR exon 21. The amplified products from nested PCR were sequenced to evaluate the feasibility of single-cell analysis for EGFR exon 21. Then, six patients diagnosed with lung adenocarcinoma whose fresh frozen specimens harbored EGFR exon 21 mutation tested by direct sequencing were chosen. All of them received gefitnib treatment and the PFS of three patients was longer than 14 months (Group A) while the PFS of other three patients was shorter than 6 months (Group B). By using the established method based on single H1975 cells, EGFR exon 21 mutational status was analyzed in single tumor cells which were captured from tumor sample by Laser Capture Microdissection (LCM). At least 20 tumor cells were captured from each tumor sample. X[2] test was used to compare the amplification rate of nested PCR and EGFR mutational rate between the two groups.
Results:
A total of 104 individual H1975 cells were obtained to detect EGFR exon 21 mutational status through the application of single-cell nested PCR. The amplification rate and allele drop-out rate were 96.2% and 7.0%. A total of 135 tumor cells from six samples were captured. The amplification rate of nested PCR was 84.3% (59/70) in Group A and 93.8% (61/65) in Group B. There was no statistical difference between the two groups (X[2] =3.119, P=0.077). The mutational rate of EGFR exon 21 L858R was 89.5% (17/19), 89.5% (17/19), and 81.0% (17/21) in the three patients in Group A and 72.2% (13/18), 68.4% (15/22), and 66.7% (14/21) in the three patients in Group B respectively. The total mutational rate was 86.4%（51/59）in Group A, which was significantly higher than the total mutational rate 68.9%（42/61）in Group B (X[2] =5.321, P=0.021).
Conclusion:
It is feasible to perform EGFR mutation detection in single cancer cells. The intratumoral heterogeneity of EGFR activating mutation in lung adenocarcinoma does exist based on the analysis in single cancer cells and the abundance of EGFR activating mutation is relevant to the benefit from EGFR-TKIs treatment.
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