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L.F. Sua
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-042 - Mutation of Epidermal Growth Factor Receptor (EGFR) in Patients with Non-Small Cell Lung Cancer (NSCLC) in a University Hospital in Latin America (ID 1457)
09:30 - 09:30 | Author(s): L.F. Sua
- Abstract
Background:
The presence of activating gene mutations in the epidermal growth factor receptor of non-small cell lung cancer patients is predictive. It improved progression-free survival and improved response rate when treated with small molecule tyrosine kinase inhibitors. Together, exon 19 deletion and exon 21 L858R gene substitution are present in about 10% of Caucasian patients and in 20–40% of Asian patients. Moreover, guidelines now suggest EGFR gene mutation testing should be conducted in all patients with lung adenocarcinoma or mixed lung cancers with an adenocarcinoma component, regardless of characteristics such as smoking status, gender or race. The success of targeted therapies in non-small cell lung cancer patients has changed the treatment paradigm in metastatic non-small cell lung cancer. We describe the frequency of mutations in exons 19 and 21 of the EGFR gene in (NSCLC) in our hospital
Methods:
Between June 2013 and March 2015, 73 samples of lung tissue of patients with NSCLC were obtained in Fundacion Valle del Lili Cali-Colombia. Microdissection cuts on paraffin-embedded lung tissue was performed with the objective of increasing the amount of tumor DNA. DNA was extracted with DNA FFPE Tissue Kit QIAamo Kit (Qiagen), then amplified with PCR and exons 19 and 20 of EGFR mutations studied for amplification. Visualization was performed using microfluidic electrophoresis in the Agilent Bioanalyzer.
Results:
We analyzed tumor samples from 73 patients with NSCLC by PCR and RFLP. Good quantity and quality of DNA in 96% (70) cases was obtained. The average age was 65.6 years ± SD, 69% (48) women and 31% (22) men. EGFR mutations were observed in 21% (15) of the samples with 80% (12) in females. 47% of mutations were in exon 19 and 53% in exon 21. 80% of cases with mutations were adenocarcinomas. 53% of patients with mutations were in stage IV disease and 33% of patients received the tyrosine kinase inhibitor.
Conclusion:
In patients who are properly selected for EGFR-positive gene mutations, EGFR-TKIs have been shown to improve symptom control and quality of life, especially in frail elderly patients who desire to avoid the systemic side effects of cytotoxic chemotherapy while achieving a certain level of clinical efficacy. As more clinical trials for novel third-generation EGFR TKIs and other alternative therapies mature, better understanding may be gained through the use of these agents in improving treatment efficacy in adenocarcinoma or even squamous cell histology of metastatic NSCLC. Figure 1
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-018 - Expression of Protein Kinase EML4-ALK Gene in Non-Small Cell Lung Cancer (NSCLC) in a University Hospital of Reference in Latin America (ID 1465)
09:30 - 09:30 | Author(s): L.F. Sua
- Abstract
Background:
Lung cancer, the leading cause of cancer deaths worldwide, exists in two distinct entities: small and non-small cell lung cancer, representing 85% of lung cancers, and generally presents at diagnosis with locally advanced or metastatic disease. The rare genetic changes, anaplastic lymphoma kinase (ALK) gene rearrangements, most often consisting in a chromosome 2 inversion leading to a fusion with the echinoderm microtubule-associated protein like 4 (EML4) gene, results in the abnormal expression and activation of this tyrosine kinase in the cytoplasm of cancer cells. This rearrangement occurs in 2–5% of NSCLC, predominantly in young patients (50 years or younger), in non-smokers or former smokers with adenocarcinoma. This aberration most commonly occurs independent of EGFR and KRAS gene mutations. Inmunohistochemical analysis is a cost-effective alternative for the detection of ALK gene rearrangements and recent guidelines from the College of American Pathologists, International Association of the Study of Lung Cancer, and The Association for Molecular Pathology supports the use of IHC screening as long as it has been appropriately validated.
Methods:
Between November 2014 and March 2015, 20 tumor samples were obtained in the Fundacion Valle del Lili, Cali-Colombia. The Ventana anti-ALK (D5F3) assay was performed using OptiView DAB IHC detection kit and OptiView Amplification Kit, with external controls rated with positive and negative cell lines (H2228 and CALU-3 respectively), with appropriate expression.
Results:
We analyzed samples from 20 patients with NSCLC using immunohistochemistry. We found tumor cells in 100% of the samples. The average age was 62.8 years ± SD, 45% (9) women and 55% (11) men. The protein kinase expression of EML4-ALK gene was found in 20% of the cases (4),which included 3 females. Thirteen cases were adenocarcinoma and fourteen patients were diagnosed in stage IV. Fourteen of twenty patients received chemotherapy. At this time in our hospital began the Phase Three study of the molecule specific for this tumor rearrangement. The mortality in this group of patients was 3 of 20.
Conclusion:
Knowledge of cancer biology and oncogenic drivers has led to a better understanding of lung cancer and the development of very active targeted therapies. ALK rearrangements have been identified as oncogenic drivers for a subgroup of lung adenocarcinoma. The clinical benefit gained by targeted therapies has led to transition from a standardized therapeutic approach to a personalized approach based on molecular tumor characteristics in current clinical practice.Figure 1
