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  P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12451

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    P3.06-011 - The impact of E-cadherin transcriptional factors on the survival of pulmonary pleomorphic carcinoma (ID 1161)

    09:30 - 09:30  |  Author(s): S. Miyahara
    • Abstract

    Background
    Pleomorphic carcinoma of the lung is a rare epithelial tumor, and its clinicopathological characteristics and prognostic factors are still controversial. Up-regulation of E-cadherin repressors is known to increase tumor cell invasion and motility in non-small cell lung cancer cells. The aim of this study was to clarify the clinicopathological characteristics and prognostic factors, such as E-cadherin repressors (e.g., Zinc finger E-box-binding homeobox [ZEB], Snail, and Twist), in pleomorphic carcinoma.

    Methods
    We reviewed 2,328 cases of resected lung cancers that occurred between 1988 and 2011 and identified 62 patients with pulmonary pleomorphic carcinoma. Immunohistochemical staining for ZEB, Snail, and Twist was performed, and nuclear expression was estimated by the percentage of positive cells. The patients were divided into two groups; a diffuse expression group (≥75%) or a focal expression group (<75%). Clinicopathological variables and the expression of E-cadherin repressors were investigated retrospectively to analyze prognostic factors for the disease-specific survival rate of 42 patients after lung resection.

    Results
    The TNM pathological stages of pleomorphic carcinoma were classified as follows: 7 (11.2%) cases with stage IA, 15 (24.1%) with stage IB, 3 (4.8%) with stage IIA, 20 (32.2%) with stage IIB, 10 (16.1%) with stage IIIA, 4 (6.4%) with stage IIIB, 3 (4.8%) with stage IV. The 5-year disease-specific survival rate after pulmonary resection was 68.3%. Forty-seven (75.8%) tumors contained at least 10% spindle and/or giant cells, and the other fifteen (24.1%) consisted entirely of spindle cells and giant cells. An adenocarcinoma component was found in 34 (54.8%) cases, a squamous cell carcinoma component in 7 (11.2%) cases, an adenosquamous cell carcinoma component in 4 (6.4%) cases, and a large cell carcinoma component in 2 (3.2%) cases. The pleomorphic carcinoma patients were divided into five groups according to the predominant epithelial component, and there were no significant differences in the disease-specific survival rate between the groups. Those with a predominance of spindle-cell or giant-cell components also showed no difference in disease-specific survival. Nuclear ZEB-1 expression was positive only in the pleomorphic component. Diffuse expression of ZEB1 was found in seven patients. Snail and Twist were positive in epithelial and pleomorphic components, but at various levels; however, expression tended to be higher in the pleomorphic component. Thirteen patients had diffuse expression of Snail, and eight had diffuse expression of Twist. Using multivariate analysis, lymph node metastasis, pleural invasion, and diffuse expression of ZEB1 in the pleomorphic component all predicted poorer disease-specific survival (p=0.007, 0.022, and 0.016, respectively). Nuclear ZEB1 expression was higher in cases with lymphatic permeation compared to those without lymphatic permeation, but this association was not statistically significant (p=0.107).

    Conclusion
    Several unfavorable prognostic factors for pulmonary plemorphic carcinoma have been reported, such as massive necrosis, TNM stages, lymph nodes metastasis, pleural invasion, and complete resection. Our current study showed that lymph node metastasis, pleural invasion, and diffuse expression of ZEB1 in the pleomorphic component suggested a worse prognosis for pulmonary pleomorphic carcinoma. ZEB1 may promote the aggressiveness and invasiveness of this malignant tumor.