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T. Umehara

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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 - 16:30  |  Author(s): T. Umehara

      • Abstract

      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.

      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.

      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).

      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.