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M. Inoue



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    P1.02 - Poster Session with Presenters Present (ID 454)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-016 - HER4 Expression Was Related to the Sensitivity of EGFR-TKI in Non-Small Cell Lung Cancer (ID 4521)

      14:30 - 14:30  |  Author(s): M. Inoue

      • Abstract

      Background:
      EGFR-TKIs show significant therapeutic effects against non-small cell lung cancer (NSCLC) with EGFR-activating mutations, however 20-30% of them have no response to EGFR-TKIs. HER-family receptors play a critical role in tumor progression, differentiation and survival in lung cancer. Recent studies suggest that the overexpression of HER-family receptors have a potential risk of EGFR-TKIs resistance. The aims of this study were to investigate the association between EGFR-mutation and the expression of HER-family receptor in regard to clinical outcomes.

      Methods:
      We invested EGFR mutation by direct PCR analysis and HER2-4 expression by immunohistochemistry (IHC) of 231 consecutive non-small cell lung cancers, who had undertaken an operation from January 2007 to July 2012. The intensity of HER2-4 was graded (score: 0-3) from negative (score: 0-1) to positive (score: 2-3). The observed protein expression levels were analyzed for correlation to EGFR mutation status, clinicopathological parameters and the responses of EGFR-TKI treatment.

      Results:
      EGFR mutation was observed in 40% of lung cancer, 61% of p. [Leu858Arg]and 31% of exon 19 deletion. Positive expression rates of HER2, HER3 and HER4 were 22.9%, 1.2%, 38.5%, respectively. HER4 positive rare of EGFR positive group was significantly higher than that of EGFR negative group (52% vs 30%, P<0.01), however there was no difference in HER2 expression. In histological type, positive rates of HER2 and HER4 in adenocarcinoma were higher than that in squamous cell carcinoma (HER2: 26% vs 13%, P=0.07, HER4: 49% vs 13%, P<0.01). HER4 positive rate of HER2 positive group was significantly lower that of HER2 negative group (43% vs 26%, P=0.03). The response rate of EGFR-TKIs in HER2 positive group was low, but high in HER4 positive group.

      Conclusion:
      Our data showed that HER4 expression was independent form EGFR mutation and HER2 expression, but related to the sensitivity against EGFR-TKIs. HER4 positive patients may be candidate for pan-HER inhibitor augments.