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Esophagus

, Volume 13, Issue 3, pp 245–253 | Cite as

Tumor-associated macrophages and angiogenesis in early stage esophageal squamous cell carcinoma

  • Youichi KumagaiEmail author
  • Jun Sobajima
  • Morihiro Higashi
  • Toru Ishiguro
  • Minoru Fukuchi
  • Kei-ichiro Ishibashi
  • Erito Mochiki
  • Koji Yakabi
  • Tatsuyuki Kawano
  • Jun-ichi Tamaru
  • Hideyuki Ishida
Original Article

Abstract

Background

The association between angiogenesis and tumor-associated macrophages (TAMs) is unclear. Mononuclear cell infiltration was reported to induce angiogenesis in early stage esophageal squamous cell carcinoma (ESCC).

Methods

The study materials included 14 samples of normal squamous epithelium, 11 samples of low-grade intraepithelial neoplasia, and 64 samples of superficial esophageal cancer (M1 and M2 cancer 27; M3 or deeper cancer 37). We assessed microvessel density (MVD) using CD34 and CD105 immunostaining and monocyte count (MC) using CD68 and CD163 immunostaining in relation to the histological type or grade of mononuclear cell infiltration, as well as the correlation between MVD and MC.

Results

MVD and MC increased in accordance with histological type, and the differences were significant (P < 0.001). MVD and MC were significantly higher in M1 and M2 lesions than in normal squamous epithelium (P < 0.05). MVD (CD34 and CD105) and MC (CD68 and CD163) were significantly correlated with the degree of mononuclear cell infiltration (P < 0.001), and there was a strong correlation between MC assessed using CD68 and MC assessed using CD163 (rS = 0.93, P < 0.001). The CD163/CD68 ratio did not differ significantly according to histological type. There was a significant correlation between MVD assessed using CD105 and MC assessed using CD68 (rS = 0.69, P < 0.001) and CD163 (rS = 0.67, P < 0.001). MVD assessed using CD34 was also significantly correlated with MC assessed using both CD68 (rS = 0.59, P < 0.001) and CD163 (rS = 0.57, P < 0.001).

Conclusion

The number of TAMs is significantly associated with the development of neovasculature in the early stage of ESCC progression.

Keywords

Microvessel density Monocyte count Tumor-associated macrophage Esophageal cancer Angiogenesis 

Abbreviations

M1

Carcinoma in situ

M2

Tumor invasion to the lamina propria mucosae

M3

Tumor invasion to the muscularis mucosa

SM1

Tumor invasion to the upper third of the submucosal layer

SM2

Tumor invasion to the middle third of the submucosal layer

SM3

Tumor invasion to the lower third of the submucosal layer

ESCC

Esophageal squamous cell carcinoma

MVD

Microvessel density

TAM

Tumor-associated macrophage

LGIN

Low-grade intraepithelial neoplasia (borderline malignancy)

Notes

Acknowledgments

This study was supported by MEXT KAKENHI Grant number 26461047.

Compliance with ethical standards

Conflict of interest

Youichi Kumagai received a research grant from MEXT KAKENHI.

Human rights statement and informed consent

All procedures followed were in accordance with the ethical standards of the committees responsible for human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent for inclusion of tissue samples in this study was obtained from all patients or their representatives.

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Copyright information

© The Japan Esophageal Society and Springer Japan 2016

Authors and Affiliations

  • Youichi Kumagai
    • 1
    Email author
  • Jun Sobajima
    • 1
  • Morihiro Higashi
    • 2
  • Toru Ishiguro
    • 1
  • Minoru Fukuchi
    • 1
  • Kei-ichiro Ishibashi
    • 1
  • Erito Mochiki
    • 1
  • Koji Yakabi
    • 3
  • Tatsuyuki Kawano
    • 4
  • Jun-ichi Tamaru
    • 2
  • Hideyuki Ishida
    • 1
  1. 1.Department of Digestive Tract and General Surgery, Saitama Medical CenterSaitama Medical UniversityKawagoeJapan
  2. 2.Department of Pathology, Saitama Medical CenterSaitama Medical UniversitySaitamaJapan
  3. 3.Department of Internal Medicine, Saitama Medical CenterSaitama Medical UniversitySaitamaJapan
  4. 4.Department of SurgeryTokyo Medical and Dental UniversityTokyoJapan

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