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The association of intravascular stromal cells with prognosis in high-grade neuroendocrine carcinoma of the lung

  • Original Article – Cancer Research
  • Published:
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Abstract

Purpose

Histological vascular invasion (VI) is major predictor of recurrence after surgery for several cancer types. We previously reported that VI with abundant stromal cell infiltrates was a negative prognostic factor in lung adenocarcinoma. This study examined whether stromal cell infiltrates within VI are associated with prognosis in high-grade neuroendocrine carcinoma (HGNEC) of the lung.

Methods

We investigated the relationship between the frequency and density of VI and recurrence-free survival (RFS) of 60 resected HGNEC patients without adjuvant chemotherapy. We examined prognostic effects of CD204 (+) macrophages, CD34 (+) microvessels and α-smooth muscle actin (+) myofibroblasts within VI. Correlation between expressions of stem cell-related molecules (ALDH-1, Notch 1, CD44) and epithelial–mesenchymal transition-related molecules (E-cadherin, S100A4) in cancer cells within VI and RFS was also analyzed.

Results

Among 60 cases, 51 cases showed VI. Although the presence of VI was a significant predictor for worse RFS (P = 0.04), the frequency and density of VI were not correlated with RFS. The number of CD204 (+) macrophage, CD34 (+) microvessels and α-smooth muscle actin (+) myofibroblasts within VI did not influence on the RFS. On the contrary, cases with higher Notch 1 expression in cancer cells in the VI displayed significantly shorter RFS than lower expression group (7.6 vs. 29.4 months, P = 0.02).

Conclusions

The current study revealed the presence of stromal cells within VI was not significant predictor for recurrence in HGNEC. This suggests that in HGNEC, unlike adenocarcinoma, intravascular stromal cells are not major contributors to metastasis.

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Abbreviations

α-SMA:

α-Smooth muscle actin

ALDH1:

Aldehyde dehydrogenase-1

CAFs:

Cancer-associated fibroblast

CI:

Confidence interval

EMT:

Epithelial-mesenchymal transition

HR:

Hazard ratio

TAMs:

Tumor-associated macrophages

VI:

Vascular invasion

VVG:

Victoria blue van Gieson

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Acknowledgments

This work was supported by the National Cancer Center Research and Development Fund (26-A-16), the Foundation for the Promotion of Cancer Research, the 3rd Term Comprehensive 10-Year Strategy for Cancer Control, the Advanced Research for Medical Products Mining Programme of the National Institute of Biomedical Innovation (NIBIO).

Authors contribution

KS and GI conceived the study. KS and SI carried out the experiments. KS and GI analyzed the data. KS, TH and GI were involved in writing the paper. All authors had final approval of the manuscript.

Author information

Authors and Affiliations

  1. Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

    Keigo Sekihara, Shinnosuke Ikemura, Koichi Saruwatari, Masahiro Morise, Takeshi Kuwata, Satoshi Fujii, Motohiro Kojima, Atsushi Ochiai & Genichiro Ishii

  2. Division of Thoracic Surgery, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

    Keigo Sekihara, Tomoyuki Hishida, Keiju Aokage, Junji Yoshida & Masahiro Tsuboi

  3. Division of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

    Shinnosuke Ikemura, Koichi Saruwatari & Masahiro Morise

  4. First Department of Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, Hamamatsu, Shizuoka, 431-3192, Japan

    Kazuhito Funai

Authors
  1. Keigo Sekihara
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  2. Tomoyuki Hishida
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  3. Shinnosuke Ikemura
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  4. Koichi Saruwatari
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  7. Satoshi Fujii
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  8. Motohiro Kojima
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  9. Atsushi Ochiai
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  11. Keiju Aokage
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  12. Junji Yoshida
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  14. Genichiro Ishii
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Corresponding author

Correspondence to Genichiro Ishii.

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Conflict of interest

The authors have no conflicts of interest to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

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Supplemental Fig. 1

Recurrence-free survival (RFS) curve of HGNEC patients according to Notch1 expression of extra-vascular cancer cells. Supplementary material 1 (PPTX 36 kb)

Supplementary material 2 (DOCX 22 kb)

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Sekihara, K., Hishida, T., Ikemura, S. et al. The association of intravascular stromal cells with prognosis in high-grade neuroendocrine carcinoma of the lung. J Cancer Res Clin Oncol 142, 905–912 (2016). https://doi.org/10.1007/s00432-015-2098-8

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  • DOI: https://doi.org/10.1007/s00432-015-2098-8

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