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T. Ishida



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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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      P1.01-020 - Expression profile of serotonin 2B receptor (HTR2B) in non-small-cell lung cancer (ID 1872)

      13:56 - 14:10  |  Author(s): T. Ishida

      • Abstract

      Background
      Recently developed molecular targeting drugs are highly effective against various cancers, however the duration of response is limited. To overcome this problem, researchers have sought to find the resistance mechanism and identify novel targets. The majority of the drugs are related to receptors tyrosine kinase (RTKs), and recently, G-protein coupled receptor (GPCR) has also been reported to play a critical role in cancer biology. We thus attempted to identify the target GPCR for the treatment of lung cancer cells.

      Methods
      We analyzed 124 patients with non-small-cell-lung cancer who had undergone surgery from January 2008 through November 2011. Expression levels of GPCR mRNA in the tumor tissues and the adjacent normal tissues were examined by comparative genomic analysis. We then sought to find the relationship between clinical features and the GPCRs that showed differential expression levels between the two types of tissues. In addition, we examined the protein levels of the GPCRs by immunohistochemistry.

      Results
      We identified 3 GPCRs and 1 related molecule. Of the 4 molecules, serotonin receptor 2B (HTR2B) was expressed higher in tumor tissues than in normal tissues. HTR2B was expressed statistically higher in the tumor tissues of female, adenocarcinoma, and non-smokers (p=0.012. 0.001, 0.045, respectively), and tended to be expressed higher in patients who harbored EGFR mutation (p=0.086). No statistically significant differences were observed in relapse-free survival. Immunohistochemistry demonstrated that HTR2B was expressed especially in the invasive front of the tumor.

      Conclusion
      Differential expression of HTR2B between cancer cells and normal tissues and its invasive potential suggest that further investigation into this molecule is needed.

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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-052 - Influence of the epidermal growth factor receptor gene mutation subtypes to the prognosis of the patients with non-small cell lung cancer (ID 3165)

      09:30 - 09:30  |  Author(s): T. Ishida

      • Abstract

      Background
      Thirty to forty percent of East Asian patients with non-small cell lung cancer (NSCLC) have epidermal growth factor receptor (EGFR) gene mutations, which are recognized as predictive factors of the response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). The most common mutations are the in-frame deletion in exon 19 and a substitution of lysine for arginine mutation at amino acid position 858 (L858R) in exon 21. It has been reported that subtype of EGFR gene mutation affects the efficacy of EGFR-TKIs in Caucasian patients with NSCLC. The deletion in exon 19 was reported to be an independent predictive factor of longer progression free survival (PFS); however, it was not a predictive factor of overall survival (OS).

      Methods
      We reviewed the records of patients with NSCLC referred to our hospital from May 2007 to May 2013, to clarify the influence of EGFR gene mutation subtype to clinical features.

      Results
      We found 128 patients with EGFR mutation, involving 124 cases of adenocarcinoma. According to the UICC-TNM ver.7, number of the patients with stage I/II disease was 59, while patients with stage III/IV was 69. We selected 60 patients with non-resectable disease (stage IIIB and IV) for the detailed analysis. The median age of the 60 patients was 74 year-old (range, 41-83). There were 39 female patients, and 39 light or never-smokers. The number of the patients with deletion mutation in exon 19 was 32 (the ratio of E746-A750 del was 78%); while the number of those with mutation in exon 21 was 24 (L858R was 96%). EGFR-TKIs were administered to 52 (86.7%) patients (erlotinib, gefitinib, and both was given in 20, 20, and 12 patients, respectively), including 35 patients without prior chemotherapy. The median duration of observation was 557 days. Any relationship between OS and clinical factor (gender, smoking history, and EGFR gene mutation subtypes) was not seen. In the patients treated with EGFR-TKIs, there was no significant difference in median OS regarding the administered drug (300 days with erlotinib or 285 days with gefitinib). In the patients with the exon 21 mutation, erlotinib-treated group had longer survival time than that of gefitinib group (200 days vs 150 days in median OS, p = 0.079). This observation was not confirmed in the patients with the exon 19 mutation.

      Conclusion
      Our retrospective analysis showed no difference of OS under subtype of EGFR gene mutation; however, the efficacy of EGFR-TKIs may differ in subtypes of EGFR gene mutation.

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    P3.10 - Poster Session 3 - Chemotherapy (ID 210)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.10-017 - The role of cytokeratin fragment antigen 21-1 ( CYFRA21-1 ) as a predictive marker for the patients with non-small-cell lung cancer treated with pemetrexed (ID 1378)

      09:30 - 09:30  |  Author(s): T. Ishida

      • Abstract

      Background
      Pemetrexed plays an important role in the treatment of advanced non-small-cell lung cancer (NSCLC). The expression of thymidylate synthase in NSCLC has been reported to be a predictive marker for patients treated with pemetrexed; however, no practical marker has been established except for histopathological features. Thus we attempted to select a practical predictive marker for pemetrexed treatment from clinical characteristics.

      Methods
      We retrospectively reviewed the charts of patients with advanced non-squamous NSCLC treated with pemetrexed in our hospital from January 2009 to December 2012. We investigated clinical variables such as smoking history, gender, clinical stage, serum tumor marker levels at the diagnosis (CEA, CYFRA21-1, ICTP, and SLX), and epidermal growth factor receptor (EGFR) mutation status. The relationships between those variables and the patients survival or response to pemetrexed were evaluated.

      Results
      We identified 60 patients, 37 male, and the average age was 65 (range, 22-83) years. There were 59 patients with adenocarcinoma. The clinical stages were; IIIA/IIIB/IV = 3/3/54 (UICC TNM ver.7). Pemetrexed with platinum (cisplatin or carboplatin) was administered to 46 patients (bevacizumab was concurrently employed in 5 patients) and 14 patients underwent pemetrexed monotherapy. When the serum CYFRA21-1 cut-off level was set at 2.1 ng/ml, the patients with low serum levels had a significantly longer progression free survival (PFS) than those with high serum levels (130 versus 263 median days; p=0.038). There was no significant difference in overall response rate and overall survival between the two groups.

      Conclusion
      High serum levels of CYFRA21-1 might reflect the higher degree of biological characteristics of squamous cell carcinoma in a tissue; therefore they could be used to identify the individuals with short PFS among patients treated with pemetrexed. Serum levels of CYFRA21-1 may become a predictive marker for advanced NSCLC patients treated with pemetrexed.