Author of

• 18974

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  P3.02 - Biology/Pathology (ID 620)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Biology/Pathology
  • Presentations: 2
  • Moderators:
  • Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23981

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    P3.02-033 - Pathological and Molecular Alterations after First and Second Generation EGFR-TKI Therapy in Patients with EGFR-Mutated Lung Adenocarcinomas (ID 8531)

    09:30 - 09:30  |  Author(s): Takeshi Fujii
    • Abstract

    Background:
    Molecular alterations, including EGFR T790M point mutation and MET gene amplification, are reported as resistance mechanisms to first and second-generation EGFR tyrosine kinase inhibitors (TKIs). However, pathological transformation after EGFR-TKI administration has not been adequately studied. We compared the pathological alterations before and after EGFR-TKI administration in patients with EGFR-mutated lung adenocarcinomas.
    
    Method:
    Between January 2016 and March 2017, 61 patients received first and second generation TKI therapy for EGFR-mutation–positive lung adenocarcinomas or adenosquamous carcinomas. Among them, 31 patients experienced recurrence, and 22 of these patients, for whom diagnosis was confirmed through re-biopsy, were included in this study. Pathological and molecular alterations in the re-biopsy specimens were analyzed for these patients. Based on the 2015 WHO classification, lepidic predominant lung adenocarcinomas were categorized as low grade, papillary or acinar lung adenocarcinoma as intermediate grade, and micropapillary or solid lung adenocarcinoma as high grade.
    
    Result:
    The EGFR T790M mutation was positive in 11 of the 22 patients. Seven patients were cytologically diagnosed by pleural and cerebrospinal fluid analysis, as well as by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA). The remaining 15 patients underwent pathologically analysis. Twelve patients were found to have adenocarcinomas, two had large-cell neuroendocrine carcinomas (LCNECs), and one displayed epithelial-mesenchymal transition (EMT). Of the 12 adenocarcinomas analyzed, eight were the same tumor grade before and after TKI therapy, and four were higher grade than before TKI therapy.Figure 1
    
    
    
    Conclusion:
    Neuroendocrine and epithelial-mesenchymal transformations have an important role in EGFR-TKI resistance mechanisms, as previous reports have shown. Regarding the re-biopsy specimens, in one third of cases, the adenocarcinomas were of a higher tumor grade than the specimens analyzed before EGFR-TKI therapy.
    
    

  • 23996

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    P3.02-048 - Clinicopathologic Characteristics of Non-Small Cell Lung Carcinomas Habouring MET Exon 14 Skipping Mutations (ID 9667)

    09:30 - 09:30  |  Presenting Author(s): Takeshi Fujii
    • Abstract

    Background:
    Non–small cell lung carcinomas (NSCLC) harboring mutations involving MET exon 14 splice sites may respond to MET inhibitors. We investigated the clinicopathologic characteristics of patients with NSCLC with MET exon 14 skipping mutations.
    
    Method:
    We examined 192 patients with NSCLC with wild-type EGFR/KRAS/ALK by reverse transcritase-polymerase chain reaction combined with SYBR Green melting curve/fragment analyses to detect the presence of MET exon 14 mutation. Clinical characteristics of MET exon 14 mutated NSCLC were compared with those of NSCLC with EGFR or KRAS mutations. MET immunohistochemistry and fluorescent in situ hybridization will be performed afterwards.
    
    Result:
    MET exon 14 mutations were identified in 21 of 192 NSCLC with wild-type EGFR/KRAS/ALK (10.9%), accounting 6.6% of all NSCLC (n=319). Patients with MET exon 14–mutated NSCLC were significantly older (median age, 77 years) than patients without MET exon 14 mutation (median, 71.5 years), and 12 (57%) were men. MET exon 14-mutated NSCLC were staged as stage 0 (n=1), stage IA (n=12), stage IB (n=4), stage IIA (n=3), or stage IV (n=1). MET exon 14–mutated NSCLC were histologically adenocarcinomas (n=20), consisting of adenocarcinoma in situ (n=1), minimally invasive adenocarcinomas (n=2), invasive adenocarcinomas (n=17) including lepidic (n=7), papillary (n=7), acinar (n=5), or solid (n=1) predominant subtypes, and adenosquamous carcinoma (n=1).
    
    Conclusion:
    MET exon 14 mutations were identified in 6.6% of all NSCLC, which may represent a clinically unique molecular subtype and an important therapeutic target in NSCLC.