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A. Takahashi

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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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      P1.06-020 - Identification of prognostic immunophenotypic features in cancer stromal cells of high-grade neuroendocrine carcinomas of the lung (ID 1760)

      09:30 - 16:30  |  Author(s): A. Takahashi

      • Abstract

      Purpose: The immunophenotypes of cancer-stromal cells have been recognized as prognostic factors of cancer. Previous reports have indicated the prognostic value of stromal cells in adenocarcinoma or non-small cell lung cancer. However, the prognostic value of stromal cells in completely resected high-grade neuroendocrine carcinomas of the lung (HGNEC; both small cell carcinoma and large cell neuroendocrine carcinoma) has not been reported. The purpose of this study was to analyze the prognostic markers of HGNEC by examining the immunophenotypes of cancer-stromal cells, including tumor-associated macrophages (TAMs), regulatory T cells (Tregs), and cancer-associated fibroblasts (CAFs).

      Materials and Methods: One hundred and fifteen patients who underwent a complete resection of HGNEC were included in this study. There were 98 men (85%), and their median age at the time of surgery was 68 years (range, 22-86 years); 71 patients had p-stage I diseases. The histologic type was SCLC in 52 patients and LCNEC in 63. We examined the presence of CD204-positive TAMs, Foxp3-positive Tregs, and podoplanin-positive CAFs to evaluate the prognostic values of these markers.

      Results: The number of CD204-positive TAMs and Foxp3-positive Tregs did not influence the overall survival (OS) or the relapse-free survival (RFS) of the patients. However, patients with podoplanin-positive CAFs had a significantly better prognosis than those with podoplanin-negative CAFs (OS: p=0.002, RFS: p=0.002, 5-year overall survival (5 YR): 74% vs. 45%). According to subgroup analyses, patients with podoplanin-positive CAFs displayed a better prognosis for both small cell carcinoma (OS: p=0.046, 5 YR: 74% vs. 46%) and large cell neuroendocrine carcinoma (OS: p=0.020, 5 YR: 74% vs. 45%). A univariate analysis identified 4 significant risk factors for OS: sex (female), pN(+), lymphatic permeation (+), and podoplanin-negative CAFs. In a multivariate analysis using the Cox regression model, sex, the presence of lymphatic permeation (ly), and podoplanin-negative CAFs were shown to be statistically significant independent predictors for recurrence.

      Conclusion: The current study reported that podoplanin-positive CAFs had prognostic value in both SCLC and LCNEC. Our results imply that podoplanin expression reflects a tumor-inhibitory phenotype of CAFs in HGNEC. Although the exact mechanisms responsible for this phenomenon are not fully understood, our results provide novel insights into the pathogenesis of a unique microenvironment of HGNEC as well as basic data for new treatment strategies for HGNEC.