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Y.W. Koh



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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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      P2.04-002 - Q787Q EGFR Polymorphism as a Prognostic Factor for Lung Squamous Cell Carcinoma (ID 1344)

      09:30 - 09:30  |  Author(s): Y.W. Koh

      • Abstract
      • Slides

      Background:
      EGFR (epidermal growth factor receptor) mutations have been frequently reported in the early stages of non-small cell lung cancer (NSCLC) and have shown survival benefits in advanced lung adenocarcinoma. However, testing for EGFR mutations have rarely been recommended for lung squamous cell carcinoma patients. Previous studies have revealed that the Q787Q polymorphism in exon 20 of the EGFR gene is associated with a poor prognosis in patients treated with gefitinib (an EGFR tyrosine-kinase inhibitor) and is frequently detected in non-adenocarcinoma lung cancer patients. There is no result for an association between Q787Q EGFR polymorphism and EGFR common mutations. The prognostic data of Q787Q EGFR polymorphism was limited to patients treated with gefitinib; therefore, prognostic information for patients without gefitinib treatment is also needed.

      Methods:
      To determine the presence of Q787Q polymorphism in patients with lung cancer, we performed direct sequencing analyses of four exons for 83 squamous cell carcinomas and 80 adenocarcinomas untreated with EGFR tyrosine-kinase inhibitors.

      Results:
      When complex mutations were excluded, the Q787Q EGFR polymorphism was more frequently detected in squamous cell carcinoma patients than adenocarcinoma patients (24% and 15.9%, respectively). The group of patients with Q787Q EGFR polymorphism included more males and heavy-smokers compared with other patient groups. The presence of the Q787Q EGFR polymorphism significantly and negatively affected the overall survival (OS) rate in patients with NSCLC (P = 0.024), particularly those with squamous cell carcinoma (P = 0.044). For stage I and II squamous cell carcinoma patients, those with the Q787Q EGFR polymorphism had lower OS rates than those with other mutations or those with a wild type phenotype (P = 0.04).

      Table 1. EGFR mutational profile of non-small cell lung carcinoma patients.
      Variable No. of patients (%)
      Exon 18
      G719X 2 (1.2%)
      T725T polymorphism 6 (3.7%)
      Exon 19 (deletion) 15 (9.2%)
      Exon 20
      Insertion 2 (1.2%)
      Q787Q polymorphism 39 (23.9%)
      Exon 21 (L858R) 19 (11.7%)
      Complex mutation
      Exon 18(T725T)+ Exon 19 (deletion) 1 (0.6%)
      Exon 19 (deletion)+ Exon 20 (Q787Q) 4 (2.4 %)
      Exon 21 (L858R)+ Exon 20 (Q787Q) 4 (2.4 %)
      Table 2. Multivariate analyses of overall survival according to clinicopathologic variables
      Variables Hazard ratio P value
      Age <60 vs. ≥60 1.836 0.021
      Sex female vs. male 2.071 0.121
      Histologic subtype Adenocarcinoma vs. Squamous cell carcinoma 0.754 0.275
      pN stage 0 vs. 1-3 1.552 0.078
      Adjuvant radiotherapy (-) vs. (+) 1.175 0.491
      Smoking grade Non-smoker
      reference
      Ex-smoker 1.907 0.144
      Light-smoker 1.378 0.452
      Heavy-smoker 1.799 0.197
      Q787Q EGFR polymorphism (-) vs. (+) 1.874 0.013


      Conclusion:
      The Q787Q EGFR polymorphism enables the stratification of pulmonary squamous cell carcinoma patients, particularly among those in stage I/II.

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