TY - JOUR
T1 - Identification of prognostic immunophenotypic features in cancer stromal cells of high-grade neuroendocrine carcinomas of the lung
AU - Takahashi, Akiko
AU - Ishii, Genichiro
AU - Kinoshita, Tomonari
AU - Yoshida, Tatsuya
AU - Umemura, Shigeki
AU - Hishida, Tomoyuki
AU - Yoh, Kiyotaka
AU - Niho, Seiji
AU - Goto, Koichi
AU - Ohmatsu, Hironobu
AU - Ohe, Yuichiro
AU - Nagai, Kanji
AU - Ochiai, Atsushi
N1 - Funding Information:
Acknowledgments 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).
PY - 2013/11
Y1 - 2013/11
N2 - Purpose 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 podoplaninpositive cancer-associated fibroblasts (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 podoplaninnegative 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. Conclusion 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.
AB - Purpose 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 podoplaninpositive cancer-associated fibroblasts (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 podoplaninnegative 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. Conclusion 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.
KW - Cancer-associated fibroblasts
KW - High-grade neuroendocrine carcinomas
KW - Large cell neuroendocrine carcinoma
KW - Regulatory T cells
KW - Small cell carcinoma
KW - Tumor-associated macrophages
UR - http://www.scopus.com/inward/record.url?scp=84892668814&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84892668814&partnerID=8YFLogxK
U2 - 10.1007/s00432-013-1502-5
DO - 10.1007/s00432-013-1502-5
M3 - Article
C2 - 24013219
AN - SCOPUS:84892668814
VL - 139
SP - 1869
EP - 1878
JO - Journal of Cancer Research and Clinical Oncology
JF - Journal of Cancer Research and Clinical Oncology
SN - 0171-5216
IS - 11
ER -