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. 2016 May;142(5):905-12.
doi: 10.1007/s00432-015-2098-8. Epub 2015 Dec 22.

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

Keigo Sekihara  1   2 , Tomoyuki Hishida  2 , Shinnosuke Ikemura  1   3 , Koichi Saruwatari  1   3 , Masahiro Morise  1   3 , Takeshi Kuwata  1 , Satoshi Fujii  1 , Motohiro Kojima  1 , Atsushi Ochiai  1 , Kazuhito Funai  4 , Keiju Aokage  2 , Junji Yoshida  2 , Masahiro Tsuboi  2 , Genichiro Ishii  5
Affiliations

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

Keigo Sekihara et al. J Cancer Res Clin Oncol. 2016 May.

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.

Keywords: High-grade neuroendocrine carcinoma; Intravascular microenvironment; Large cell neuroendocrine carcinoma; Notch1; Small cell lung cancer; Stromal cells; Vascular invasion.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Representative images of VI in HGNEC. Victoria blue van Gieson (a) and HE (b) of small cell carcinoma. Victoria blue van Gieson (c) and HE (d) of large cell neuroendocrine carcinoma
Fig. 2
Fig. 2
Survival analyses of HGNEC patients. a Recurrence-free survival (RFS) curves according to the number of VI) (cutoff level 3). b RFS curves according to the density of VI (cutoff level 1.3/cm2)
Fig. 3
Fig. 3
Immunohistochemical staining of Notch1 and α-smooth muscle actin (SMA) in HGNEC. a SCLC with Notch1 positive within VI. b SCLC with Notch1 negative within VI. c LCNEC with α-SMA-positive myofibroblasts within VI. d SCLC without α-SMA-positive myofibroblasts within VI
Fig. 4
Fig. 4
Recurrence-free survival (RFS) curve of HGNEC patients according to Notch1 expression in cancer cells within VI
See this image and copyright information in PMC

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