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X. Shi



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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
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      P2.01-050 - Clinicopathological Characteristics of PD-L1 Expression in Lung Adenocarcinoma (ID 4562)

      14:30 - 14:30  |  Author(s): X. Shi

      • Abstract

      Background:
      Lung adenocarcinoma (AD) is a common variant lung cancer, accounting for about 70% of non-small cell lung cancer. PD1/PD-L1 is a promising immune therapy target which has achieved promising results in the late stage NSCLC patients in the ongoing clinical trials. Because of different accompanying diagnostic antibodies employed in different clinical trials and limited data regarding PD-L1 expression in the small number of patients enrolled in clinical trials, there is an urgent need to examine the expression of PD-L1 in lung cancer samples in order to enrich patients who will benefit from the immune targeted therapy. Our goal was to detect PD-L1 expression and analyze its expression with the clinicopathological characteristics.

      Methods:
      Protein expression of PD-L1 was examined by immunohistochemistry method using the VENTANA PD-L1 (SP263) rabbit monoclonal antibody. Messenger RNA level of PD-L1 was evaluated by in situ hybridization method. Tissue microarrays (TMAs) containing formalin fixed paraffin embedded (FFPE) lung adenocarcinoma cases were used in this study.

      Results:
      This study included 133 cases of lung AD totally. PD-L1 expression rate in lung ASC was 16.5% at the mRNA level and 13.5% at the protein level, which the kappa coefficient of the two examination methods was 0.824 (P=0.000, highly correlated). PD-L1 expression in lung AD was found to be highly expressed in female patients and smokers (P=0.019 and 0.002), while no association was identified between PD-L1 expression and age, tumor size, clinical stage, positive pleural invasion, histological type (lepidic or non-lepidic type), lymph node metastasis or therapy methods. Overexpression of PD-L1 was a significantly indicator of shorter recurrence free survival (RFS) time and overall survival duration (P=0.000 and 0.000). Multivariate analysis revealed that PD-L1 expression was an independent risk factor for poor RFS and overall survival (P=0.004 and 0.006).

      Conclusion:
      PD-L1 overexpression is more frequently observed in smokers in lung adenocarcinoma. PD-L1 expression is an indicator of worse prognosis in surgically resected lung adenocarcinoma patients.

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    P2.03b - Poster Session with Presenters Present (ID 465)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 2
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      P2.03b-021 - Screening for Major Oncogene Alterations in Adenosquamous Lung Carcinoma Using PCR Coupled with Next-Generation and Sanger Sequencing Methods (ID 3917)

      14:30 - 14:30  |  Author(s): X. Shi

      • Abstract

      Background:
      Despite progress in personalized lung adenocarcinoma treatment, development of efficacious molecular targeted therapies for adenosquamous cell carcinoma (ASC) of the lung has made little progress because of limited knowledge concerning gene mutation status and the rarity of this type of tumor.

      Methods:
      We examined the frequency of EGFR, K-Ras, B-Raf, PIK3CA, DDR2, ALK, and PDGFRA gene mutation using NGS, PCR, and Sanger sequencing methods in ASC samples. Macrodissection or laser microdissection was performed in 37 cases to separate adenomatous and squamous components of ASC for further sequencing. Fifty-six patients who underwent operations in Peking Union Medical College Hospital between January 2010 and December 2014 were enrolled in the study.

      Results:
      The overall mutation rate was 64.29%, including 55.36%, 7.14%, and 1.79% for EGFR, K-Ras, and B-Raf mutations, respectively. PIK3CA mutation was detected in three cases; all involved coexisting EGFR mutations. Of the 37 cases, 34 were convergent in two components, while three showed EGFR mutations in the glandular components and three showed PIK3CA mutations in the squamous components. With respect to EGFR mutations, the number of young female patients, nonsmokers, and those with positive pleural invasion was higher in the mutation-positive group than that in the mutation-negative. K-Ras mutation was significantly associated with smoking. Overall survival in the different EGFR mutation groups differed significantly.Figure 1



      Conclusion:
      The frequency and clinicopathological characteristics of EGFR- and KRAS-mutated adenosquamous lung carcinoma were similar to that noted in Asian adenocarcinomas patients. The high convergence mutation rate in both adenomatous and squamous components suggests monoclonality in ASC.

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      P2.03b-087 - PD-L1 Expression in Adenosquamous Lung Carcinoma and the Comparison with the Other Common Variants of Non-Small Cell Lung Cancer (ID 3992)

      14:30 - 14:30  |  Author(s): X. Shi

      • Abstract

      Background:
      Adenosquamous lung carcinoma (ASC) is a hybrid tumor made of adenocarcinoma and squamous cell carcinoma in one tumor. It is a rare disease with poorer prognosis comparing with the other common variants of non-small cell lung cancer (NSCLC). There is a persisting need for identifying more effective targeted therapy methods. Immune check point therapy targeted PD-1 or PD-L1 has achieved promising results in advanced stage NSCLC. PD-L1 expression has been suggested as a potential biomarker to enrich patients who will benefit from these treatments. There is limited data regarding the expression of PD-L1 in lung ASC and its correlation with the driver oncogene changes.

      Methods:
      Protein expression of PD-L1 was examined by immunohistochemistry method using the VENTANA PD-L1 (SP263) Rabbit Monoclonal Antibody. Messenger RNA level of PD-L1 was evaluated by in situ hybridization method. EGFR, K-ras, and B-raf mutation were detected by real time PCR method. Tissue microarrays (TMAs) containing formalin fixed paraffin embedded (FFPE) NSCLC cases were used in this study.

      Results:
      This study included 51 cases of lung ASC, 133 cases of lung adenocarcinoma (AD), and 83 cases of lung squamous cell carcinoma (SCC), totally. PD-L1 expression rate in lung ASC at the mRNA level and the protein level is highly correlated, which the kappa coefficient of the two examination methods is 0.856 (P=0.000). For the 46 cases of lung ASC, which the glandular and squamous components were analyzed separately, PD-L1 expression were divergent and mainly occurred in the SCC component of lung ASC. PD-L1 expression rate in the SCC component of ASC is similar with the result of lung SCC (39% vs 29%, P=0.327); its expression rate in AD component of ASC is the same with the result of lung AD (13.7% vs 13.5%, P=1.000). There is no association between PD-L1 expression and clinicopathological characteristics in lung ASC, for example, sex, age, smoking status, clinical stage, prognosis, EGFR mutation, K-ras mutation, or B-raf mutation, et al.

      Conclusion:
      PD-L1 expression in the two components of lung ASC is divergent and more prone to be expressed in the SCC component. Lung ASC may be not suitable for the PD-L1 targeted therapy because of this divergent expression status.