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R. Okita

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    P1.01 - Poster Session 1 - Cancer Biology (ID 143)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.01-010 - Heterogeneity of biomarkers between the primary tumor and the metastatic lymph nodes in non-small cell lung cancer (ID 1203)

      09:30 - 16:30  |  Author(s): R. Okita

      • Abstract

      Recently, the personalized treatments for non-small cell lung cancer (NSCLC) have progressed with the understanding of the biology and the molecular mechanisms of the tumor. Treatment strategy is determined based on the biomarker profiles examined with the primary tumor tissue or the metastatic lymph nodes. However, because tumor cells acquire the metastatic phenotype through the process of clonal evolution occurring during the tumor progression, there could be the heterogeneity of the biomarker profiles between the primary tumor and the metastatic lesions. The aim of this study was to investigate the heterogeneity of the biomarkers between the primary tumor and the metastatic lymph nodes, and to evaluate the clinical significance of its discordancy.

      Seventy-two patients of NSCLC with lymph node metastases who underwent complete resection with systematic lymph node dissection between 2004 and 2010 were studied. The study was conducted with the approval of the institutional ethics committee. Immunohistochemical analysis of ERCC1 and VEGF and the mutation analysis of EGFR were performed with the paraffin-embedded tissue of both the primary tumor (PT) and the metastatic lymph nodes (LN).

      There were 47 male and 25 female, with the median age of 69.4 years. Thirty-eight patients had adenocarcinoma, 23 had squamous cell carcinoma, and 11 had other histologic types of NSCLC. Twenty-nine patients had N1 disease, and 43 had N2. Median observation period was 35.7 months. The 5-year overall survival rate of 72 patients was 38.0%, with 53.2% in N1 cases and 28.8% in N2 cases. ERCC1 was positive in 41.7% of PT and 58.3% of LN. There were 34 cases (47.2%) with the discordant expression of ERCC1. VEGF was positive in 66.7% of both PT and LN, whereas 32 cases (44.4%) were discordant. EGFR mutation was detected in 31.9% of PT and 18.1% of LN. There were 10 cases (13.9%) with discordant mutation status. All 10 cases had mutant EGFR in PT, whereas EGFR mutation was not found in LN. Of the 49 patients with EGFR mutation-negative in PT, none showed mutations in LN. There were no differences in relapse-free survival and overall survival among the biomarker profile groups. Among patients who had negative ERCC1 in PT or LN, overall survival was significantly better in patients who received platinum-based chemotherapy perioperatively compared with that in patients who did not. However, there were no differences in patients with positive ERCC1 in PT or LN. Seventeen patients who had mutant EGFR in PT were treated with gefitinib. The responses were CR in 4, PR in 7, SD in 2, and PD in 4, with the response rate of 64.7% and the disease control rate of 76.5%. All the nine patients who had mutant EGFR in both PT and LN showed disease control, whereas 4 out of 8 patients who had mutant-negative EGFR in LN showed PD.

      It should be noted that discordancy of biomarker profiles between PT and LN was not a few. Understanding the heterogeneity of biomarkers would be essential for the establishing the personalized treatments for NSCLC.