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J Cancer Res Clin Oncol. 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.

Author information

1
Pathology Division, Department of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa-City, Chiba, 277-8577, Japan.

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.

PMID:
24013219
DOI:
10.1007/s00432-013-1502-5
[Indexed for MEDLINE]

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