Esophagus

, Volume 15, Issue 1, pp 19–26 | Cite as

Thymidine phosphorylase and angiogenesis in early stage esophageal squamous cell carcinoma

  • Youichi Kumagai
  • Tetsuhiko Tachikawa
  • Morihiro Higashi
  • Jun Sobajima
  • Akemi Takahashi
  • Kunihiko Amano
  • Minoru Fukuchi
  • Kei-ichiro Ishibashi
  • Erito Mochiki
  • Koji Yakabi
  • Jun-ichi Tamaru
  • Hideyuki Ishida
Original Article
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Accepted:
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Abstract

Background

The relationship between thymidine phosphorylase (TP) and angiogenesis at the early stage of esophageal squamous cell carcinoma has been unclear.

Methods

Using 14 samples of normal squamous epithelium, 11 samples of low-grade intraepithelial neoplasia, and 64 samples of superficial esophageal cancer, microvessel density (MVD) was estimated using immunostaining for CD34 and CD105. TP expression was also evaluated in both cancer cells and stromal monocytic cells (SMCs). We then investigated the correlation between MVD and TP expression in both cancer cells and SMCs.

Results

On the basis of the above parameters, MVD was significantly higher in cancerous lesions than in normal squamous epithelium. In terms of CD34 and CD105 expression, MVD showed a gradual increase from normal squamous epithelium, to low-grade intraepithelial neoplasia, and then to M1 and M2 cancer, and M3 or deeper cancer. M1 and M2 cancer showed overexpression of TP in both cancer cells and SMCs. There was no significant correlation between TP expression in cancer cells and MVD estimated from CD34 (rS = 0.16, P = 0.21) or CD105 (rS = 0.05, P = 0.68) expression. Significant correlations were found between TP expression in SMCs and CD34-related (rS = 0.46, P < 0.001) and CD105-related (rS = 0.34, P < 0.01) MVD. In M3 or deeper cancers, there were no significant correlations between TP expression in cancer cells or SMCs and venous invasion, lymphatic invasion, and lymph node metastasis.

Conclusion

TP expression is activated in both cancer cells and stromal monocytic cells at the very early stage of ESCC progression. TP expression in SMCs, rather than in cancer cells, is significantly correlated with angiogenesis.

Keywords

Thymidine phosphorylase Microvessel density Monocyte count 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

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Notes

Acknowledgements

Youichi Kumagai received MEXT KAKENHI Grant number 26461047.

Compliance with ethical standards

Ethical Statement

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.

Conflict of interest

Youichi Kumagai received MEXT KAKENHI Grant number 26461047.

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Copyright information

© The Japan Esophageal Society and Springer Japan KK 2017

Authors and Affiliations

  • Youichi Kumagai
    • 1
  • Tetsuhiko Tachikawa
    • 2
  • Morihiro Higashi
    • 3
  • Jun Sobajima
    • 1
  • Akemi Takahashi
    • 2
  • Kunihiko Amano
    • 1
  • Minoru Fukuchi
    • 1
  • Kei-ichiro Ishibashi
    • 1
  • Erito Mochiki
    • 1
  • Koji Yakabi
    • 4
  • Jun-ichi Tamaru
    • 3
  • Hideyuki Ishida
    • 1
  1. 1.Department of Digestive Tract and General Surgery, Saitama Medical CenterSaitama Medical UniversityKawagoeJapan
  2. 2.Division of Molecular Diagnosis and Cancer PreventionSaitama Cancer CenterSaitamaJapan
  3. 3.Department of Pathology, Saitama Medical CenterSaitama Medical UniversitySaitamaJapan
  4. 4.Department of Internal Medicine, Saitama Medical CenterSaitama Medical UniversitySaitamaJapan

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