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

Keigo Sekihara, Tomoyuki Hishida, Shinnosuke Ikemura, Koichi Saruwatari, Masahiro Morise, Takeshi Kuwata, Satoshi Fujii, Motohiro Kojima, Atsushi Ochiai, Kazuhito Funai, Keiju Aokage, Junji Yoshida, Masahiro Tsuboi, Genichiro Ishii

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)905-912
Number of pages8
JournalJournal of Cancer Research and Clinical Oncology
Volume142
Issue number5
DOIs
Publication statusPublished - 2016 May 1
Externally publishedYes

Fingerprint

Neuroendocrine Carcinoma
Stromal Cells
Blood Vessels
Lung
Recurrence
Survival
Myofibroblasts
Microvessels
Smooth Muscle
Actins
Macrophages
Neoplasms
Cadherins
Adjuvant Chemotherapy
Adenocarcinoma
Stem Cells

Keywords

  • High-grade neuroendocrine carcinoma
  • Intravascular microenvironment
  • Large cell neuroendocrine carcinoma
  • Notch1
  • Small cell lung cancer
  • Stromal cells
  • Vascular invasion

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The association of intravascular stromal cells with prognosis in high-grade neuroendocrine carcinoma of the lung. / Sekihara, Keigo; Hishida, Tomoyuki; Ikemura, Shinnosuke; Saruwatari, Koichi; Morise, Masahiro; Kuwata, Takeshi; Fujii, Satoshi; Kojima, Motohiro; Ochiai, Atsushi; Funai, Kazuhito; Aokage, Keiju; Yoshida, Junji; Tsuboi, Masahiro; Ishii, Genichiro.

In: Journal of Cancer Research and Clinical Oncology, Vol. 142, No. 5, 01.05.2016, p. 905-912.

Research output: Contribution to journalArticle

Sekihara, K, Hishida, T, Ikemura, S, Saruwatari, K, Morise, M, Kuwata, T, Fujii, S, Kojima, M, Ochiai, A, Funai, K, Aokage, K, Yoshida, J, Tsuboi, M & Ishii, G 2016, 'The association of intravascular stromal cells with prognosis in high-grade neuroendocrine carcinoma of the lung', Journal of Cancer Research and Clinical Oncology, vol. 142, no. 5, pp. 905-912. https://doi.org/10.1007/s00432-015-2098-8
Sekihara, Keigo ; Hishida, Tomoyuki ; Ikemura, Shinnosuke ; Saruwatari, Koichi ; Morise, Masahiro ; Kuwata, Takeshi ; Fujii, Satoshi ; Kojima, Motohiro ; Ochiai, Atsushi ; Funai, Kazuhito ; Aokage, Keiju ; Yoshida, Junji ; Tsuboi, Masahiro ; Ishii, Genichiro. / The association of intravascular stromal cells with prognosis in high-grade neuroendocrine carcinoma of the lung. In: Journal of Cancer Research and Clinical Oncology. 2016 ; Vol. 142, No. 5. pp. 905-912.
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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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T1 - The association of intravascular stromal cells with prognosis in high-grade neuroendocrine carcinoma of the lung

AU - Sekihara, Keigo

AU - Hishida, Tomoyuki

AU - Ikemura, Shinnosuke

AU - Saruwatari, Koichi

AU - Morise, Masahiro

AU - Kuwata, Takeshi

AU - Fujii, Satoshi

AU - Kojima, Motohiro

AU - Ochiai, Atsushi

AU - Funai, Kazuhito

AU - Aokage, Keiju

AU - Yoshida, Junji

AU - Tsuboi, Masahiro

AU - Ishii, Genichiro

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N2 - 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.

AB - 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.

KW - High-grade neuroendocrine carcinoma

KW - Intravascular microenvironment

KW - Large cell neuroendocrine carcinoma

KW - Notch1

KW - Small cell lung cancer

KW - Stromal cells

KW - Vascular invasion

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