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Robert L. Keith

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    P3.03 - Biology (Not CME Accredited Session) (ID 969)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
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    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.03-25 - Squamous Cell Carcinoma-Associated Bronchial Dysplasias Demonstrate Altered T-helper Lymphocyte Differentiation (ID 13998)

      12:00 - 13:30  |  Author(s): Robert L. Keith

      • Abstract
      • Slides


      Persistent bronchial dysplasia (BD) is associated with an increased risk for development of invasive squamous cell carcinoma and demonstrates altered polarization of inflammatory cell subsets by gene expression analysis as compared to BD that regresses. We hypothesized that a decrease in the T-helper 1 (Th1) to T-helper 2 (Th2) lymphocyte ratio would be associated with progression to invasive squamous cell carcinoma (SCC).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      VECTRA 7-color multispectral staining was applied to formalin fixed paraffin embedded (FFPE) persistent (N=12) and regressive (N=10) BD that also included four biopsies from patients that subsequently developed SCC (3 persistent and 1 regressive, 2 from the actual site of progression). inForm (Perkin-Elmer) image analysis software was used to enumerate cells that showed double positivity for Tbet-CD4 (Th1) and GATA3-CD4 (Th2) and the ratios of the percentage of Th1 and Th2 cells amongst all CD4 positive cells were calculated from multiple lesional fields for each BD (dysplastic epithelium and underlying stroma). DNA extracted from the full remaining FFPE tissue of four of these cases were sequenced employing the Oncomine Comprehensive v3 NGS panel (ThermoFisher) and the number of somatic mutations and variant allele frequencies (VAF) were determined using a threshold of at least 200 total reads and 25 variant reads per variant identified.

      4c3880bb027f159e801041b1021e88e8 Result

      A decreased Th1:Th2 ratio was seen in SCC-associated BD as compared to BD from patients that did not develop lung cancer (p=0.04; ratio = 0.04 vs. 0.68, respectively). No significant difference was seen in persistent versus regressive BD groups. There was an inverse correlation between Th1:Th2 ratios and mutational load (r2=0.21) and VAF (r2=0.28) although the small number of specimens precluded identification of a statistically significant relationship.

      8eea62084ca7e541d918e823422bd82e Conclusion

      A decreased Th1:Th2 ratio is associated with BD from subjects that progress to SCC suggesting that alterations in T-helper lymphocyte differentiation may contribute to progression. A potential inverse relationship between Th1:Th2 ratios and mutational load or mutant clonal expansion (increased VAF) will require further study.


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