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Journal of Cancer Research and Clinical Oncology

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01-11-2013 | Original Paper

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

Authors: 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

Published in: Journal of Cancer Research and Clinical Oncology | Issue 11/2013

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 podoplanin-positive 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 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.

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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Title: Identification of prognostic immunophenotypic features in cancer stromal cells of high-grade neuroendocrine carcinomas of the lung
Authors: 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
Publication date: 01-11-2013
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 11/2013
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-013-1502-5

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