Identification of prognostic immunophenotypic features in cancer stromal cells of high-grade neuroendocrine carcinomas of the lung

Akiko Takahashi, Genichiro Ishii, Tomonari Kinoshita, Tatsuya Yoshida, Shigeki Umemura, Tomoyuki Hishida, Kiyotaka Yoh, Seiji Niho, Koichi Goto, Hironobu Ohmatsu, Yuichiro Ohe, Kanji Nagai, Atsushi Ochiai

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1869-1878
Number of pages10
JournalJournal of Cancer Research and Clinical Oncology
Volume139
Issue number11
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Neuroendocrine Carcinoma
Stromal Cells
Lung
Survival
Neoplasms
Large Cell Carcinoma
Small Cell Carcinoma
Recurrence
Macrophages
Regulatory T-Lymphocytes
Cancer-Associated Fibroblasts
Multivariate Analysis

Keywords

  • Cancer-associated fibroblasts
  • High-grade neuroendocrine carcinomas
  • Large cell neuroendocrine carcinoma
  • Regulatory T cells
  • Small cell carcinoma
  • Tumor-associated macrophages

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Identification of prognostic immunophenotypic features in cancer stromal cells of high-grade neuroendocrine carcinomas of the lung. / Takahashi, Akiko; Ishii, Genichiro; Kinoshita, Tomonari; Yoshida, Tatsuya; Umemura, Shigeki; Hishida, Tomoyuki; Yoh, Kiyotaka; Niho, Seiji; Goto, Koichi; Ohmatsu, Hironobu; Ohe, Yuichiro; Nagai, Kanji; Ochiai, Atsushi.

In: Journal of Cancer Research and Clinical Oncology, Vol. 139, No. 11, 2013, p. 1869-1878.

Research output: Contribution to journalArticle

Takahashi, A, Ishii, G, Kinoshita, T, Yoshida, T, Umemura, S, Hishida, T, Yoh, K, Niho, S, Goto, K, Ohmatsu, H, Ohe, Y, Nagai, K & Ochiai, A 2013, 'Identification of prognostic immunophenotypic features in cancer stromal cells of high-grade neuroendocrine carcinomas of the lung', Journal of Cancer Research and Clinical Oncology, vol. 139, no. 11, pp. 1869-1878. https://doi.org/10.1007/s00432-013-1502-5
Takahashi, Akiko ; Ishii, Genichiro ; Kinoshita, Tomonari ; Yoshida, Tatsuya ; Umemura, Shigeki ; Hishida, Tomoyuki ; Yoh, Kiyotaka ; Niho, Seiji ; Goto, Koichi ; Ohmatsu, Hironobu ; Ohe, Yuichiro ; Nagai, Kanji ; Ochiai, Atsushi. / Identification of prognostic immunophenotypic features in cancer stromal cells of high-grade neuroendocrine carcinomas of the lung. In: Journal of Cancer Research and Clinical Oncology. 2013 ; Vol. 139, No. 11. pp. 1869-1878.
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abstract = "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.",
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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

PY - 2013

Y1 - 2013

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

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