Author of

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  P2.01 - Poster Session with Presenters Present (ID 461)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Biology/Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 17483

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    P2.01-085 - Epigenetic Profile of Oligoprogressive versus Widespread Non-Small Cell Lung Cancer Patients (ID 4669)

    14:30 - 14:30  |  Author(s): M.D.N. Juárez Rusjan
    • Abstract
    • Slides

    Background:
    Lung cancer is the worldwide leading cause of death from cancer. Epigenetic silencing of tumor suppressor genes (TSG) contributes to the development and progression of lung cancer. In this prospective study we assess the methylation profile of locally advanced and oligometastatic versus widespread metastatic Non-Small Cell Lung Cancer (NSCLC). We will determine the ability of a panel of tumor suppressor genes (TSG) to discriminate these clinical phenotypes
    
    Methods:
    Patients (≥18 years) were eligible for inclusion if they had histologically confirmed unresectable non-pretreated stage III/IV NSCLC. Paraffin-embedded blocks from patients from this study cohort were macro-dissected based on hematoxylin-eosin evaluations to ensure a minimum of 75% of tumor cells. DNA was extracted. Promoter methylation status of TSG (SFRP5, TIMP3, HLTF, RUNX3, ID4) will be evaluated by EpiTect Methyl II Signature PCR (Qiagen). Data analysis was done using integrated Excel-based templates, which provide gene methylation status as percentage unmethylated (UM) and percentage methylated (M) fraction of input DNA. Methylation levels were described as: ³1-19%: low methylation level, 20-59%: moderate methylation level and ³60%: high methylation level. Presence of intrathoracic disease and limited extrathoracic disease, (M1b, proposed 8th TNM edition) vs multiple metastatic disease (M1c) was described for clinical and molecular analysis.
    
    Results:
    From March 2015 to June 2016, 40 out of 60 sixty patients had enough tissue to be included. Intrathoracic disease was present in 19 patients (47.5%), M1b disease in 8(20%) and 13 patients (32.5%) had multiple extrathoracic disease. The methylation profile for intrathoracic disease was: SFRP5 was found in 4/19 patients (21.1%), ID4 7/19 (36.6%), HLTF 12/19 (63.2%), RUNX3 19/19 (100%) and TIMP3 10/19 (52.6%); for M1b disease: SFRP5 was found in 4/8 patients (50%), ID4 3/8 (37.5%), HLTF 6/8 (75%), RUNX3 6/8 (75%) and TIMP3 7/8 (87.5%); for M1c disease: SFRP5 6/13 patients (46.2%), ID4 9/13 (69.2%), HLTF 11/13 (84.6%), RUNX3 13/13 (100%) and TIMP3 8/13 (61.5%). Overall survival was shortened for the group of patients with methylation of ID4³20% (14.5 vs 19 months, p=0.010 Log Rank Test). In the subgroup analysis this difference was sustained for patients with oligoprogressive disease (Intrathoracic plus IVb) vs IVc (9.5 vs 17.5 months, p=0.05 Log Rank Test vs 14 vs 19 months , p=0.51, respectively)
    
    Conclusion:
    Although no definitive conclusions can be done because of the sample size, it seems that patients with methylation of ID4 of 20% or more have worse prognosis. ID4 could also help to differentiate oligometastatic vs widespread NSCLC
    
    

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