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Y. Zenke



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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
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      P3.06-016 - Aldehyde dehydrogenase 1 expression in cancer cells could have prognostic value for patients with non-small cell lung cancer who are treated with neoadjuvant therapy: identification of prognostic microenvironmental factors after chemoradiation (ID 1726)

      09:30 - 09:30  |  Author(s): Y. Zenke

      • Abstract

      Background
      Prognostic biomarkers for patients with non-small cell lung cancer (NSCLC) who have been treated with neoadjuvant therapy have not been fully assessed. Identifying biological prognostic markers may help to distinguish patients who are likely to benefit from additional postoperative chemotherapy. The purpose of this study was to analyze prognostic biomarkers in surgically resected NSCLC after treatment with neoadjuvant therapy, with special reference to the immunophenotypes of both the cancer cells and the stromal cells.

      Methods
      A series of 66 patients with NSCLC who were treated with neoadjuvant chemotherapy, chemoradiotherapy, or radiotherapy followed by complete resection at our hospital between April 1992 and December 2009 were reviewed. Among the 66 surgically resected specimens, case with viable tumor cells remained in the specimens were included in this study (n =52). We examined the expressions of geminin and cleaved caspase 3 (proliferation and apoptosis markers), E-cadherin and vimentin (epithelial mesenchymal transition related molecules), ALDH1 and CD44v6 (Stem cells related molecules) in the cancer cells. Furthermore in the stromal cells, the expressions of podoplanin and CD90 in cancer associated fibroblasts (CAFs) and CD204 in tumor associated macrophages (TAMs) were also examined.

      Results
      The 5-year disease-free survival rate of patients with high ALDH1 expression levels in their cancer cells was significantly lower than those with a low ALDH1 level (47.3% vs. 21.5%, respectively; P =0.023). The expression statuses of geminin, cleaved caspase 3, E-cadherin, vimentin, and CD44v6 in the cancer cells had no prognostic impact. The 5-year disease-free survival rate of patients with low or high podoplanin and CD90 levels in CAFs and CD204 levels in TAMs expression levels were not any prognostic impact in the stromal cells (37.9% vs. 29.1%, 33.8% vs. 37.5%, 38.4% vs. 29.0%, P =0.90, P = 0.75, P =0.98). In NSCLC without neoadjuvant therapy matching for clinical stage and histopathology (case control, n =104), the 5-year DFS rate of the patients with a high ALDH1 expression level was 48.3%, while that of the cases with a low ALDH1 expression level was 59.8%. The expression of ALDH1 in cancer cells was not correlated with the prognosis in NSCLC without neoadjuvant therapy (P =0.507). A multivariate analysis identified ALDH1 expression in cancer cells as significantly independent prognostic factors for disease-free survival in patients who received neoadjuvant therapy (P =0.045).

      Conclusion
      The presence of ALDH1-positive cancer cells was an independent recurrence predictor in patients who received neoadjuvant therapy, while CAFs and TAMs did not provide any predictors. Although prospective studies with a larger number of patients are required to confirm the prognostic significance of ALDH1 expression in cancer cells in validation populations with neoadjuvant therapy, our results suggest that the immunophenotypes of ALDH1 expression can serve as a guide to additional treatment after surgical resection in patients who received neoadjuvant therapy.