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M. Krasnik



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    P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.06-022 - Population based study of the prevalence of EGFR mutations in non-small cell lung cancer (NSCLC) (ID 1979)

      09:30 - 09:30  |  Author(s): M. Krasnik

      • Abstract

      Background
      Activating mutations in the EGFR gene identifies NSCLC patients sensitive to treatment with EGFR tyrosine kinase inhibitors. EGFR mutations are more prevalent in Asians compared to Caucasian. However, estimates of mutation frequencies are only available from selected patient cohorts and the incidence in an unselected Caucasian population is unknown. This study assess the prevalence of EGFR mutations in an unselected population based cohort, and the correlation between mutation and gender, age, ethnicity, smoking habits, as well pathological data.

      Methods
      Patients diagnosed with NSCLC June 1, 2010 - September 30, 2011 in a well-defined population of 1.7 million in the Capital Region, Denmark, were included in this single center study. The type and location of the diagnostic material was registered. All specimens were pretreatment, no residual tumors were included. Smoking data were also available. The mutation analyses were investigated by therascreen EGFR RGQ PCR Kit (detection of 29 somatic mutations in the EGFR oncogene, Qiagen) (n =1121) or direct sequencing (n=62). Twenty-two patients were analyzed with both methods.

      Results
      658 men and 598 women were included. All but 4 were Caucasians. 6.2% were never smokers, 38.9% were ex- smokers and 54.9% were current smokers. 1161 (92.4%) patients had material sufficient for mutation analysis. More than 50% malignant tumor cells were available for analyses in 68%, 76% and 56% of the histological, cytological clot, and cytological smear material respectively. Manual macro dissection to ensure this high concentration of tumor cells was done on 32%, 4%, and 10% of the histological, cytological clots, and cytological smears material, respectively. Cytological material was used for 38 % of the mutation analyses. 5.4 % of tested patients harbored mutation in the EGFR gene (4.3% men/ 6.7 % women). The majority of mutations (55 cases= 87%) were activating mutations (29 exon 19 deletions, 24 L858R mutations and 2 G719X mutations), 3 were rare mutations (two L861Q and one S768I) with unclear clinical response to TKI, five were insertions in exon 20 (resistance mutation). Three of the mutations (all exon 19 deletions) were detected in the three included Asian women. 8.0 % of adenocarcinomas, 1.9% of squamous cell carcinomas and one single case of adenosquamous cell carcinoma were mutated. No other tumor types were mutated. DNA yield was similar whether extracted from cytological or histological samples and these material types yielded similar mutation percentages (6.55% in cytology and 4.66% in histology of material analyzed). 29.4%, 4.4% and 2.9 % of never, ex- and current smokers, respectively, were mutated (p<0.001). No significantly difference between ex- and current-smokers was observed. Mutation status was not related to age.

      Conclusion
      EGFR mutations analysis on cytological as well as on histological material was possible in 92% of patients with NSCLC. 5.4% of the patients harbored EGFR mutation. Adenocarcinomas were mutated more often (8.0%) than squamous cell carcinomas (1.9%). Mutations were found in never smokers as well as in former and current smokers. No difference in gender and age regarding mutation status was observed.