Identification of prognostic immunophenotypic features in cancer stromal cells of high-grade neuroendocrine carcinomas of the lung
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The immunophenotypes of cancer stromal cells have been recognized as prognostic factors of cancer. The purpose of this study was to analyze the prognostic markers of high-grade neuroendocrine carcinomas of the lung (HGNEC; both small cell carcinoma and large cell neuroendocrine carcinoma) by examining the immunophenotypes of cancer stromal cells.
Materials and methods
One hundred and fifteen patients who underwent a complete resection of HGNEC were included in this study. We examined the presence of CD204-positive tumor-associated macrophages (TAMs), Foxp3-positive regulatory T cells (Tregs), and podoplanin-positive cancer-associated fibroblasts (CAFs) to evaluate the prognostic values of these markers.
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 (5YR): 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, 5YR: 74 vs. 46 %) and large cell neuroendocrine carcinoma (OS: p = 0.020, 5YR: 74 vs. 45 %). Moreover, in multivariate analyses, the podoplanin status of the CAFs was shown to be a statistically significant independent predictor of recurrence.
The presence of podoplanin-positive CAFs had a favorable prognostic value, suggesting that the evaluation of podoplanin expression by CAFs would lead to a novel risk classification of patients.
KeywordsSmall cell carcinoma Large cell neuroendocrine carcinoma High-grade neuroendocrine carcinomas Cancer-associated fibroblasts Tumor-associated macrophages Regulatory T cells
This work was supported by National Cancer Center Research and Development Fund (23-A-12 and 23-K-18), the Foundation for the Promotion of Cancer Research, 3rd-Term Comprehensive 10-Year Strategy for Cancer Control, Program for the Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation, and JSPS KAKENHI (24659185).
Conflict of interest
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