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D. Zhong
Author of
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-002 - Concurrent EGFR T790M Secondary Mutation and EMT in a Lung Adenocarcinoma Patient with EGFR TKI Drug Resistance (ID 7373)
09:30 - 09:30 | Author(s): D. Zhong
- Abstract
Background:
Almost all EGFR-mutant lung cancers develop resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). Several mechanisms for this acquired resistance have been identified, including development of an EGFR T790M mutation, MET amplification, hepatocyte growth factor (HGF) overexpression, loss of PTEN expression, epithelial to mesenchymal transition (EMT) and transformation to small cell lung cancer.
Method:
We presented a lung cancer patient with EGFR exon 19 deletion who was resistant to EGFR TKI treatment during disease progression. The original lung tumor started to enlarge and bred a secondary growing nodule adjacently. A left upper lobectomy plus systematic mediastinal lymphadenectomy by VATS was performed after a whole body evaluation which had no sign of extrapulmonary abnormalities. The pathological examination, genetic sequencing, and histological staining of E-cadherin and Vimentin were performed on the TKI resistant postoperative specimens.
Result:
The original lung tumor was confirmed to be adenocarcinoma according to the typical morphology and positivity of TTF1 and CK7. The secondary lung tumor has sarcomatoid histology showing a more spindle-like mesenchymal morphology with CK and Vimentin positivity. Next generation sequencing (NGS) test confirmed that the original lung adenocarcinoama retained EGFR exon 19 deletion but was also found T790M mutation in EGFR exon 20. The secondary sarcomatoid carcinoma retained EGFR exon 19 deletion as well. Besides, sarcomatoid carcinoma had genetic mutation on FANCL and BCL2L2, and amplification on CDK4, MDM2, APFRP1, GNAS, CIC, FANCE, Notch4 and AKT2. In addition, in comparison with adenocarcinoma from biopsy and postoperative specimens, the second growing sarcomatoid tumor is strongly positive for Vimentin and nearly negative for E-cadherin, indicating that sarcomatoid histology probably underwent EMT.
Conclusion:
The clinical implication of this case provides significant insights into our understanding that two or more mechanisms might be involved simultaneously in the EGFR TKI resistance. Therefore, if possible, it is necessary to perform tumor biopsies after the development of resistance to identify the best treatment options for patients.
