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A.M. Marini



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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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      P2.04-041 - Characterization of EGFR Activating Mutations in Brazilian Patients with Pulmonary Adenocarcinoma (ID 1596)

      09:30 - 09:30  |  Author(s): A.M. Marini

      • Abstract
      • Slides

      Background:
      The presence of EGFR activating mutations in pulmonary adenocarcinoma is predictive of exquisite response to EGFR-tyrosine kinase inhibitors. Here we studied the frequency of EGFR activating mutations in pts consecutively treated in our institution.

      Methods:
      It is a retrospective, uniinstitutional study of all consecutively tested samples from pts diagnosed with pulmonary adenocarcinoma and treated in our Institute. All samples were formalin-fixed and paraffin-embedded. Tumor areas were selected and macrodissected, followed by whole DNA extraction and amplification by PCR. EGFR genotyping was performed through DNA sequencing (exons 18, 19, 20 and 21) by Sanger´s methodology.

      Results:
      417 pts had tumor samples genotyped between Aug/2011 and Sep/2015. Median age was 62 y (17-91), 237 (57%) female. According to ethnicity, 357 pts were Caucasian (86%), 37 African-American (9%) and 21 Asian (5%); 140 pts were classified as never-smokers (34%), 37 (9%) as light-smokers (≤ 10 p.y.) and 238 (57%) as current smokers/> 10 p.y.. EGFR activating mutations could be identified in 103 out of 417 samples (24.7%): 78 were exon 19 deletions (76%), 23 were L858R mutation in exon 21 (22%), and two were rare mutations (G719S in exon 18, and V774M and S768I in exon 20). These mutations were found to be more frequent in females than in males (32% vs. 15%, p=0.0001), and in never-smokers and light-smokers than in current smokers/> 10 p.y. (65% vs. 16%, p<0.0001). It is noteworthy to mention that EGFR mutations were detected in 31 current smokers/> 10 p.y. pts. With the exception of 2 cases, all tumors harboring EGFR activating mutations presented TTF-1 expression by immunohistochemistry, and among those TTF-1-negative adenocarcinomas, no mutation was detected in 36/38 samples (p=0.0011). In a median follow-up of 12 months, the median overall survival was 16.3 months among those pts with stage IV and ECOG-PS 0-1, whose tumors presented EGFR-activating mutations.

      Conclusion:
      In this Brazilian pts, the frequency of EGFR activating mutations was 28%, being more frequent in females, and never-smokers or light smokers. These results reinforce the importance of diagnosing EGFR activating mutations in all pts with TTF-1-positive, pulmonary adenocarcinoma.

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