Author of

• 12769

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  P3.18 - Poster Session 3 - Pathology (ID 177)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12781

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    P3.18-012 - The hidden 50% of the ALK positive NSCLC patients (ID 2469)

    09:30 - 09:30  |  Author(s): N. Peled
    • Abstract

    Background
    Patients with lung adenocarcinoma carrying the ALK gene rearrangement show dramatic response to ALK TKIs (e.g. crizotinib). The currently approved method for detection of ALK gene rearrangements is fluorescence in situ hybridization (FISH), however gene sequencing can also be used for detecting ALK rearrangement. Aberrant ALK protein expression, as ALK is not normally expressed in the lung, can be detected with immunohistochemistry (IHC). Our experience has shown a high rate of false negative ALK FISH patients, therefore we retrospectively investigated 53 cases with IHC and Next Generation Sequence (NGS).

    Methods
    53 patients with NSCLC adenocarcinoma were tested for ALK rearrangement by FISH (Oncotest-TEVA Ltd, Israel). Retrospective IHC (D5F3 antibody, Cell Signaling) was done at the University of Colorado Cancer Center. Discordance cases were sequenced by "FoundationOne” (Foundation Medicine Inc).

    Results
    Out of the 53 cases, 4 (7.5%) were FISH positive, and 8 (15%) were IHC positive with 3 cases both FISH+ and IHC+ (Figure 1 , Table 1). One specimen was FISH+ and IHC-. NGS was performed on the 5 IHC+/FISH- mismatched samples and found 4 out of the 5 cases positive for ALK rearrangement. The true positive incidence of ALK rearrangement in our cohort increased by 100%, from 7.5% to 15%. Interestingly, two patients were found to harbor a unique ALK rearrangement at intron 19. One of them showed a dramatically improvement to crizotinib (PFS=18 months).

    FISH	IHC	Patients	NGS	ALK rearrangement +
    +	+	3		3
    -	-	44		0*
    +	-	1(1.8%)		0
    -	+	5(9.4%)	4	4
    Total		53	4	7

    Table 1 - FISH and IHC summary Figure 1

    Conclusion
    The current FISH based approach to detect ALK gene rearrangement misses numerous (50%) patients who might benefit from the most efficient lung cancer therapy for their disease. Screening for ALK protein expression by IHC may identify ALK positive patients that would otherwise be missed. Borderline IHC staining should be further sequenced by NGS to cover other abnormalities such as intron19 or other uncommon rearrangements.