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C. Phanthunane



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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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      P2.04-017 - The Study of a Relationship between Thyroid Transcription Factor-1 Expression and EGFR Mutations in Unselected Thai Patients with NSCLC (ID 778)

      09:30 - 09:30  |  Author(s): C. Phanthunane

      • Abstract
      • Slides

      Background:
      Epidermal growth factor receptor (EGFR) mutation status is a important test to guide treatment with EGFR tyrosine kinase inhibitors (EGFR TKI) effectively. However mutation detection by DNA direct sequencing remains expensive and is not readily available for routine practice in advanced NSCLC in Thailand. Thus a simple alternative method of EGFR mutation detection is required in NSCLC treatment. Recent studies have demonstrated a good association of Thyroid Transcription Factor-1 (TTF-1) with common TKI-sensitive EGFR mutations in NSCLC. We investigated the possibility of the routine test of TTF-1 expression by a simple immunohistochemistry (IHC) method as a potential indicator of common TKI-sensitive EGFR status in unselected Thai patients with non-small cell lung cancer.

      Methods:
      We collected tissue sample from 91 patients with NSCLC whose EGFR mutation status had previously been detected by DNA direct sequencing from January 2010 to January 2015. TTF-1 was detected by immunohistochemistry method. Results of expression of TTF-1 staining were scored as two categories were negative (no immunostaining or <5% stained cells) and positive (more than 5% positive cells with unequivocal nuclear immunostaining).

      Results:
      A total of 91 NSCLC samples with available results of molecular-based EGFR mutational status were collected. The common TKI-sensitive EGFR mutation was detected in 38/91 cases (42%) which included Exon19 del in 18/91 cases (20%), Exon 21 (L858R) point mutations in 20/91 cases (22%). The others 4 cases were found with uncommon EGFR mutations included Exon 20 (T790M), Exon18 (G719X), Exon 20 S768I and Exon 20 ins. There was 1 case with EGFR mutations at both Exon18 (G719X) and 20 ins. No mutation detected (wild-type, WT) were found in 48/91 patients. Of all 91 tissue samples were available for TTF-1 IHC testing, 80 of 91 patients were positive for TTF-1 (88%). For 80 patients with adenocarcinoma histology and 10 patients with squamous cell carcinoma history, TTF-1 was positive in 93% and 60 % respectively (P<0.05). The expression of TTF-1 in EGFR 19 del and 21 exon (L858R) mutation groups were significantly higher than the WT group (95% vs 81%, P < 0.05). In only 1 of 38 specimens positive for EGFR mutations was TTF-1 negative. The sensitivity was 97 % and specificity was 17%. Estimated negative predictive values (NPV) of TTF-1 expression for common TKI-sensitive EGFR mutation prevalence rates of 42% was 90%.

      Conclusion:
      These results indicated that positive TTF-1 expression has a significant positive correlation with common TKI-sensitive EGFR mutation at exon 19 and 21. In high prevalence area of EGFR mutation positive in Thailand, TTF-1 could be a valuable marker of EGFR mutation status.

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