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T. Fujishita



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    MO21 - Prognostic and Predictive Biomarkers V - EGFR (ID 98)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO21.04 - Prognostic and Therapeutic Implications of the Aromatase Expression in Lung Adenocarcinoma Harboring EGFR Mutation (ID 2242)

      10:30 - 12:00  |  Author(s): T. Fujishita

      • Abstract
      • Presentation
      • Slides

      Background
      A significantly greater proportion of females and adenocarcinoma patients is found in never-smoking NSCLC groups than in smoking NSCLC groups. Recent studies have demonstrated that estrogens may contribute to the carcinogenesis and development of lung carcinoma. In the present study, we investigate the correlation between the expression of aromatase (CYP19-1) and clinicopathologic factors and assess the prognostic significance of the aromatase expression in patients with primary lung adenocarcinoma.

      Methods
      The aromatase mRNA expression levels in the primary tumors and corresponding nonneoplastic lung specimens of 110 Japanese patients who underwent complete resection for primary lung adenocarcinoma were evaluated using quantitative RT-PCR. The relationships between the aromatase expression and clinicopathologic factors or survival were analyzed. To test the growth inhibitory effects of the aromatase inhibitor exemestane alone and in combination with the EGFR-TKI erlotinib in vitro, the cell proliferation of the lung adenocarcinoma cell lines HCC4006 and 11-18 was measured according to the WST-8 method.

      Results
      The mRNA expression level of aromatase in the carcinoma tissues was significantly higher than that in the corresponding normal lung tissues (P = 0.013). The aromatase expression in the lung adenocarcinoma tissues was not correlated with the clinicopathologic factors, including patient gender, age, smoking status, EGFR mutation status or pathologic stage. A high aromatase expression was associated with a poor prognosis in terms of both the recurrence-free survival (RFS) (P = 0.004) and overall survival (OS) (P = 0.003). A multivariate analysis showed that the aromatase expression was a significant prognostic factor, with a relative risk of 2.35 (P = 0.043) for RFS and 5.19 (P = 0.004) for OS. We further stratified the population according to gender, smoking status and EGFR mutation status. A high aromatase expression was related to a poor prognosis in femles (RFS; P = 0.008, OS; P < 0.001), never-smokers (RFS; P = 0.009, OS; P < 0.001) and patients with EGFR mutations (RFS; P = 0.005, OS; P = 0.003). A multivariate analysis showed that the aromatase expression was a significant prognostic factor, with a relative risk of 5.22 (P = 0.013) for RFS in the patients with EGFR mutations. HCC4006, harboring an EGFR mutation with a low aromatase mRNA expression, was not sensitive to exemestane alone or combination with erlotinib. In contrast, 11-18, harboring an EGFR mutation with a high aromatase mRNA expression, was sensitive to exemestane alone. In addition, cell growth was significantly inhibited by the combination of exemestane and erlotinib.

      Conclusion
      A high expression of aromatase is correlated with a poor outcome in patients with lung adenocarcinoma, especially those harboring EGFR mutations. Aromatase may be a therapeutic target in lung adenocarcinoma with a high aromatase expression and with an EGFR mutation.

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    P1.12 - Poster Session 1 - NSCLC Early Stage (ID 203)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.12-015 - Prognostic impact of the amount of tobacco smoking in patients with resected non-small cell lung cancer (ID 2258)

      09:30 - 16:30  |  Author(s): T. Fujishita

      • Abstract

      Background
      The purpose of this study was to investigate the relationship between the amounts of tobacco smoking and the clinicopathological features of non-small cell lung cancer (NSCLC) patients.

      Methods
      We retrospectively reviewed the clinical records of 1825 consecutive NSCLC patients who underwent surgery in our department. Among them, the data sets of 363 squamous cell carcinoma (Sq) patients and 720 adenocarcinoma (Ad) patients who received lobectomy or more extensive resection were available. The definitions of smokers used in the study were: light smoker had a smoking history of 30 pack-years (PY) or less, heavy smokers had a history of more than 30 to 60 PY and super-heavy smokers had a history of more than 60 PY. The survival curves were estimated according to the Kaplan-Meier method and were assessed by the log-rank test. A multivariate survival analysis was performed using the Cox proportional hazards model. Differences were considered to be statistically significant for values of P < 0.05.

      Results
      There were more male patients, more aggressive operations (bi-lobectomy or pneumonectomy) and heavier smokers in the Sq patients than Ad patients (p< 0.0001, p=0.012 and p<0.0001). In Ad patients, the never-smokers (n=309) were more likely to be female, to have less advanced stage tumors and had a significantly better prognosis than ever-smokers (n= 441) (five-year OS: never-smokers, 67.9%; smokers, 53.7%, p<0.0001). In Sq patients, the never-smokers (n=15) were more likely to be female than the ever-smokers (n=348). There was no significant prognostic difference between never-smokers and ever-smokers in the Sq patients (five-year OS: never-smokers, 28.6%; ever-smokers, 46.7%, p=0.36). Among ever-smokers, the light-smokers (n=56) had more female patients, more advanced stage tumors and a significantly worse prognosis than heavy smokers (n=292) (p = 0.0003). The multivariate survival analysis showed that light smoking was related to a worse prognosis compared to heavy smoking (HR=2.06, 96%CI 1.43-2.98, p=0.0001).

      Conclusion
      The never-smokers had a better prognosis than ever-smokers in Ad patients, whereas the light-smokers (PY ≤ 30) had a significantly worse prognosis than heavier smokers (PY > 30) in Sq patients. There might be other factors than tobacco carcinogens that influence the development of squamous cell carcinoma in light smokers.