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Jane Sze Yin Sui



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    P2.02 - Biology/Pathology (ID 616)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.02-048 - Survival Correlation Between TP53 Gene and PD-L1 Tumour Expression in Resected Non-Small Cell Lung Carcinoma (ID 10272)

      09:30 - 16:00  |  Presenting Author(s): Jane Sze Yin Sui

      • Abstract

      Background:
      Tumour suppressor gene TP53 mutation is common in human cancers, especially playing an important role in lung cancer tumourgenesis. Some clinical studies have shown that TP53 alterations in non-small cell lung carcinoma (NSCLC) carry a worse prognosis and may relatively more resistant to chemotherapy and radiation. We conducted this study to evaluate the impact of TP53 assessed by limited targeted profiling, correlating with PD-L1 tumour expression and clinicopathological variables in resected NSCLC.

      Method:
      NSCLC patients who underwent curative resection between 1998 and 2006 at our institution were included. PD-L1 status was assessed using Ventana SP142 antibody on archival FFPE surgical tumour specimens, arrayed on tissue microarrays (TMAs) with triplicate 0.6 mm cores. PD-L1 was scored as positive if membranous staining was present in >1% of tumour cells aggregated across the replicate cores to address heterogeneity. In collaboration with the Lung Cancer Genomics Ireland Study, a targeted panel of 49 genes was assessed by Sequenom MassArray including TP53 and genes in MAPK and PI3K pathways. Clinicopathological data was obtained from hospital electronic database.

      Result:
      Seventy-two patients were included, of which 40 (58.0%) were males, with a median age of 66.0 years (range: 51.0 – 82.6). 54.2%, n=39 with adenocarcinoma histological subtypes, 45.8%, n=33 were ex-smoker and 42.9%, n=30 had Stage IB disease. Most patients had T2 stage (71.4%, n=50), N0 nodal disease (55.2%, n=37) and grade 2 differentiation (65.7%, n=46). Presence of TP53 mutation was identified in 22 patients (30.5%). Five patients had co-presence of TP53 mutation and PD-L1 positivity. There was no correlation between PD-L1 positivity with TP53 status, KRAS, PTPN11, PHLPP2, PIK3CA, MET and PIK3R1. The median disease-free survival in TP53 mutation with PD-L1 positivity was not reached. In univariate/unadjusted analysis, co-presence of TP53 mutation and PD-L1 positivity appear to have superior disease-free survival over TP53 wild-type and PD-L1 negativity, HR 0.17 (95%CI 0.01-0.78, p=0.018). A trend was seen with overall survival but not statistically significant (TP53 mutant, PD-L1 positive vs TP53 wild-type, PD-L1 negative: NR vs 23.1 months, HR 0.34 (95% CI: 0.0.5-1.11, p=0.079). Independent PD-L1 positivity appears to be associated with better prognosis: DFS HR 0.36 (95% CI 0.11-0.90, p=0.0272) and OS HR 0.47 (95% CI 0.19-0.98, p=0.0427).

      Conclusion:
      In our cohort, co-presence of TP53 mutation and PD-L1 expression was not associated with poorer survival among resected NSCLC patients. Independently, PD-L1 expression was associated with better survival, a finding which warrants further investigations as potential biomarker.