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. 2013 Nov;139(11):1869-78.
doi: 10.1007/s00432-013-1502-5. Epub 2013 Sep 7.

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

Akiko Takahashi  1 , Genichiro Ishii, Tomonari Kinoshita, Tatsuya Yoshida, Shigeki Umemura, Tomoyuki Hishida, Kiyotaka Yoh, Seiji Niho, Koichi Goto, Hironobu Ohmatsu, Yuichiro Ohe, Kanji Nagai, Atsushi Ochiai
Affiliations

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

Akiko Takahashi et al. J Cancer Res Clin Oncol. 2013 Nov.

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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Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Immunohistochemical staining for CD204, Foxp3, and podoplanin in high-grade neuroendocrine carcinoma (HGNEC) of the lung. a A case with high CD204-positive tumor-associated macrophages (TAMs). b A case with low CD204-positive TAMs. c A case with high Foxp3-positive regulatory T cells (Tregs). d A case with low Foxp3-positive Tregs. e A case with podoplanin-positive cancer-associated fibroblasts (CAFs). f A case with podoplanin-negative CAFs
Fig. 2
Fig. 2
Survival analysis of HGNEC patients with CD204-positive TAMs, Foxp3-positive Tregs, and podoplanin-positive CAFs. a Overall survival curves according to CD204 expression in TAMs. b Relapse-free survival curves according to CD204 expression in TAMs. c Overall survival curves according to Foxp3 expression in Tregs. d Relapse-free survival curves according to Foxp3 expression in Tregs. e Overall survival curves according to podoplanin expression in CAFs. f Relapse-free survival curves according to podoplanin expression in CAFs
Fig. 3
Fig. 3
Survival analysis of HGNEC patients without postoperative chemotherapy. a Overall survival curves. b Relapse-free survival curves
Fig. 4
Fig. 4
Subgroup analysis combining podoplanin expression in CAFs and other independent risk factors. Group A: ly (−)/podoplanin-positive CAFs; Group B: ly (+)/podoplanin-positive CAFs or ly (−)/podoplanin-negative CAFs; and Group C: ly (+)/podoplanin-negative CAFs)
See this image and copyright information in PMC

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