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D. Lazo



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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
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      P2.04-095 - Detection of Mutations in Tumor and Blood Samples from Lung Adenocarcinoma Patients Using Two Different Techniques (ID 2278)

      09:30 - 09:30  |  Author(s): D. Lazo

      • Abstract

      Background:
      Adenocarcinoma is currently the most common type of lung cancer in which genetic alterations with prognostic and predictive value have been identified. EGFR mutations are predictive of response to TKI and mutually exclusive with KRAS mutation. Molecular analyses from tissue biopsies are nowadays mandatory in initial pathology studies and recommended if TKI resistance develop. Molecular analysis in circulating cell-free DNA (cfDNA) appeared as an easier method to perform these studies. cfDNA analysis from plasma or serum in lung cancer have identified mutations in EGFR, KRAS, ALK and HER-2, that correlated with those observed in the primary tumor. This study compared two different techniques to determine KRAS and EGFR mutations in tissue and blood samples from patients with lung adenocarcinoma.

      Methods:
      Patients with suspected lung cancer admitted to Clinica Las Condes between October 2012 and March 2014, were offered to enter the Study. Previous to biopsy, 20ml of blood was drawn and samples of plasma and serum stored. When an adenocarcinoma was diagnosed EGFR and KRAS mutations of the biopsy were analyzed by COBAS[®] KRAS/EGFR Mutation Tests and by SSCP (Single Stranded Conformational Polymorphism) and confirmed by Sanger sequencing. Blind analysis of stored plasma and serum was performed, isolating cfDNA using QIAamp[®] Circulating Nucleic Acid kit, and tumor DNA by QIAamp[®] DNA FFPE Tissue kit. Clínica Las Condes Ethics Board approved the study, and informed consent obtained in all patients.

      Results:
      Twenty-one patients entered the study; two were excluded because final pathology showed Atypic Hyperplasia. Of the reminding 19 patients: 14 had invasive Adenocarcinoma, 3 in situ Adenocarcinoma and 2 Adenosquamous carcinoma. Tissue biopsies were obtained from the primary tumor in 14 cases, pleural metastases in 2, lymphnode metastases in 2 and brain metastases in one. Two patients had Adenocarcinoma in situ, 10 stage I, 1 stage II, 2 stage III and 4 stage IV. Seven patients have mutations detected by COBAS[®] and SSCP in tissue biopsies: 3 EGFR and 4 KRAS mutations. EGFR mutations were detected in 2 stage I, and one stage IV patients. KRAS in 1 ACAis, 2 stage I and one stage IV. In these patient´s plasma only 1 mutation was detected in cfDNA (KRAS mutation in one stage IV patient), correlation between tissue biopsy and cfDNA 1 out of 7 (14%). No mutations were detected in cfDNA from serum samples.

      Conclusion:
      In our study EGFR and KRAS mutations rates were lower than expected for Chilean population, but it could be due to the small sample size. We had poor general correlation between mutations in tissue biopsies compared with those detected in cfDNA (14%). In stage IV correlation was better (50%). No EGFR mutations were detected in cfDNA, but again could be due to the sample size. COBAS[®] technique was useful to determine KRAS mutations in plasma cfDNA. Both SSCP and COBAS techniques allow determining mutations in tumor samples. cfDNA analysis could be used to determine KRAS mutations in patients with advanced disease. Its use to determine EGFR mutations need to be investigated in larger studies.