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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
EGFR MUTATIONS IN NON-SMALL CELL LUNG CANCER: LOCAL EPIDEMIOLOGY AND CLINICAL IMPORTANCE
Introduction:
Lung cancer's dismal prognosis led to new therapeutic approaches among which TKIs being among most promising;
Material And Method:
Retrospective study at the Regional Institute of Oncology Iasi of non small cell lung cancer patients which underwent molecular investigations between November 2013 - September 2014. EGFR mutation status (positive, negative, undetermined) was assessed with an Entrogen EGFR kit using DNA extracted from paraffin embedded samples (surgical or endobronchial biopsies) with the Macherey-Nagel "NucleoSpin FFPE DNAkit" and then amplified on a Applied Biosystem 7500 Real Time PCR System.
Results:
There were 63 adenocarcinoma samples (17 females, mean age 60,9 +/- 9 years): 49 primary lung tumors and 14 secondary lesions (brain, lymph nodes, pleural). There was insufficient bioptic material for three cases. TTF1 status was determined for 46 patients--six were negative. There were twelve mutations identified (7 female subjects, 5 male)--six L858R, five Del 19 and one G719X; ten were TTF1 positive for the remaining two TTF1 status was unknown. Female sex predominance was statistically significant (p = 0.02, chi squared). Mean age for mutation positive patients was 64 +/- 10 years; there were three never smokers, three active smokers and no data on smoking status was available for six subjects.
Conclusion:
Although small dimension of the study group precludes statistical significance EGFR mutations seem to correlate with TTF1 status.
Insights
Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients may correlate with thyroid transcription factor 1 (TTF1) status. Further research is needed due to the small study size.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung cancer presents a poor prognosis, driving the development of novel therapies.
- Tyrosine Kinase Inhibitors (TKIs) are among the most promising therapeutic strategies for lung cancer.
Purpose of the Study:
- To investigate the correlation between EGFR mutation status and TTF1 status in non-small cell lung cancer (NSCLC) patients.
- To assess the prevalence of EGFR mutations in a cohort of NSCLC patients.
Main Methods:
- Retrospective study of 63 NSCLC patients undergoing molecular investigations.
- EGFR mutation status assessed using an Entrogen EGFR kit and real-time PCR.
- DNA extracted from paraffin-embedded tumor samples (biopsies).
Main Results:
- Twelve EGFR mutations were identified (6 L858R, 5 Del 19, 1 G719X) in 63 adenocarcinoma samples.
- TTF1 status was determined for 46 patients; ten mutations were TTF1 positive.
- Female sex was a statistically significant factor (p = 0.02).
Conclusions:
- EGFR mutations appear to correlate with TTF1 status in NSCLC.
- The small study size limits definitive statistical significance.
- Further investigation is warranted to confirm these findings.
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