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M. Aoki



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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-009 - Expression of BMP-7 in non-small cell lung cancer and its clinical significance (ID 1108)

      09:30 - 09:30  |  Author(s): M. Aoki

      • Abstract

      Background
      Bone morphogenetic protein-7 (BMP-7) is signaling molecule belonging to the transforming growth factor (TGF) - beta superfamily. Expression of BMP-7 is highest in the kidney and it is thought to be related to kidney and eye development and skeletal patterning. Recent studies demonstrated that BMP-7 was expressed in various human cancers. However, there have been few reports detailing this in non-small cell lung cancer (NSCLC). Then, the purpose of the present study was to investigate expression of BMP-7 in clinical samples of NSCLC to determine its clinicopathological and prognostic impact.

      Methods
      160 NSCLC patients who received complete resection at Kagoshima University Hospital from 2001 to 2007 were enrolled in the study. Two patients underwent pneumonectomy, 4 bilobectomy, 154 lobectomy. A total of 160 patients were classified, including 102 male and 58 female patients (range, 26- 84 years; average, 69 years). The final pathological examination disclosed that cases of stage IA, IB, IIA, IIB, IIIA NSCLC numbered 50, 52, 16, 15 and 27, respectively. The patients were histopathologically classified as 112 adenocarcinoma, 40 squamous cell carcinoma or 8 others (adenosquamous carcinoma, large cell carcinoma, mucoepidermoid carcinoma, pleomorphic carcinoma) according to the 7[th] Edition of General Rule for Clinical and Pathological Record of Lung Cancer (The Japan Lung Cancer Society, 2010). Expression of BMP-7 in cancer　tissue was evaluated by immunohistochemistry. Correlations between expression of BMP-7 and clinicopathological factors and prognosis were analyzed retrospectively. The study was approved by the Institutional Review Board of Kagoshima University and performed according to the Helsinki Declaration. A statistical analysis of group differences was performed using χ[2] test. The Kaplan-Meier method was used for survival analysis and evaluated by the log-rank test. The Cox proportional hazard model was used in multivariate analysis. p<0.05 was considered statistically significant.

      Results
      Immunohistochemically, in NCSLC, BMP-7 expression was identified in cell membranes but also in the cytoplasm of cancer cells. The patients were classified into two groups (BMP-7-positive group, 68 cases; BMP-7-negative group, 92 cases). Expression of BMP-7 correlated with T factor (p=0.047), N factor (p=0.013) and pathological stage (p=0.046). BMP-7 expression was significantly correlated with overall survival after the operation (p=0.003). Moreover, multivariate analysis revealed BMP-7-positivity as an independent prognostic factor (p=0.022).

      Conclusion
      We can use BMP-7 expression as a predictor of lymph node metastasis and postoperative outcome in NSCLC. The signals activated by BMP-7 are complicated and involve intracellular and extracellular factors, so further analysis seems to be necessary to determine the mechanism involved.

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    P3.07 - Poster Session 3 - Surgery (ID 193)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P3.07-002 - Pleural lymph flows exceeding the lung segment (ID 65)

      09:30 - 09:30  |  Author(s): M. Aoki

      • Abstract

      Background
      Limited pulmonary resections including lung segmentectomy for peripheral small lung cancer have attracted attention in recent years. However, a surgical consensus has not been established. It has been pointed out that there are not only lymph flows to pulmonary hilum along pulmonary vessels or bronchi but also pleural lymph flows directory into the mediastinum or adjacent lung lobe. There are some lung cancer cases with pleural indentation less than twenty millimeters. In these cases, it is concerned that lymph flows carry metastases from the pulmonary segment directly into the mediastinal lymph nodes without passing through the hilar lymph nodes. In other words, skip metastases might be caused. However, there have been few reports investigating pleural lymph flows exceeding the lung segment. The present study was designed to evaluate whether pleural lymph flows exceeding the lung segment could be detected using indocyanine green (ICG) and a fluorescence imaging system intraoperatively.

      Methods
      Fourteen patients undergoing lung segmentectomy or lobectomy for a tumor were enrolled in this study. A jet ventilation is selectively applied under bronchofiberscopy to the burdened bronchus to develop an anatomic border between the inflated segment to be evaluated and the deflated area. A 1.0 ml solution containing the fluorescent dye ICG (2.5 mg/ml) was injected into three to five subpleural sites of the segment. Fluorescence imaging device (HyperEye Medical System, MIZUHO IKAKOGYO CO.,LTD. Tokyo, Japan) was used to monitor the ICG-containing lymph flows from the injection site for five minutes. We evaluated the presence of pleural lymph flows exceeding the lung segment.

      Results
      We observed pleural lymph flows in eight of fourteen cases (57.1%), and pleural lymph flows exceeding the lung segment in seven of fourteen cases (50.0%). There is no pleural lymph flow from superior segment of bilateral lower lobe exceeding the segment in studies of several segments. Figure 1

      Conclusion
      Pleural lymph flows exceeding the lung segment can be observed in vivo. Skip metastases may occur through subpleural lymph channels in subpleural lung cancer cases. We should pay attention to skip metastases when we perform limited pulmonary resections for such cases.