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Hassana Fathallah



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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-129 - Potential Impact of KRAS Molecular Profiling of Non-Squamous Non-Small Cell Lung Cancer (NSCLC). (ID 14472)

      16:45 - 18:00  |  Author(s): Hassana Fathallah

      • Abstract

      Background

      Several studies suggest that patients with KRAS-mutant (KRASmut) NSCLC fail to benefit from platinum-based systemic chemotherapy and are not likely to have targetable mutations. Molecular profiling has the potential to identify other potential targets that might provide novel therapy for KRASmut NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In this study, we purified RNA from archived tumors of patients with stage I and II NSCLC wild-type (wt) and mutant (Mut) KRAS and from paired normal tissue from 20 and 17 patients, respectively, and assessed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) the expression of four genes involved in DNA synthesis and repair including thymidylate synthase (TS), BRCA1, ECCR1, RAP80, and the proto-oncogene, SRC. Additionally, we assessed expression of PD-L1 IHC 22C3 by immunohistochemistry using an antibody against PD-L1 IHC 22C3.

      4c3880bb027f159e801041b1021e88e8 Result

      Our results show that in KRASmut tumors, ERCC1, TS, and SRC expression were increased in comparison to paired normal lung tissue (p ≤ 0.04). Expression of BRCA1 and RAP80 were similar in both KRASmut tumor and the paired-normal tissue. Furthermore, expression of BRCA1, TS and SRC were significantly increased in KRASwt tumor relative to their expression in normal lung (p ≤ 0.044). Expression of ERCC1 and RAP80 were similar in KRASwt tumors and paired normal tissue. Interestingly, SRC expression in KRASmut tumor was decreased in comparison to KRASwt tumor. There was a notable expression of PD-L1 (cut off level of 50%) in the tumor and surrounding stromal cells in 2 out of 20 KRASmut tumors.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In conclusion, within the limitation of our retrospective study, KRASmut NSCLC would likely be platinum, taxane and pemetrexed resistant, having a low level of PD-L1 expression. KRAS wt BRCA1 positive tumors tend to be sensitive to taxane therapy and possibly platinum-based drugs. Our result suggests the need to develop targeted therapies for KRASmut NSCLC and other therapies specific to the molecular profile of the tumor.

      ERCC1 BRCA1 TS SRC PD-L1 (50%)
      mt.Kras + - + - 10%
      Wt.Kras - + + +
      Normal Lung Tissue - - - -

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