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Thymidine phosphorylase and angiogenesis in early stage esophageal squamous cell carcinoma

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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.

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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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Acknowledgements

Youichi Kumagai received MEXT KAKENHI Grant number 26461047.

Author information

Authors and Affiliations

  1. Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan

    Youichi Kumagai, Jun Sobajima, Kunihiko Amano, Minoru Fukuchi, Kei-ichiro Ishibashi, Erito Mochiki & Hideyuki Ishida

  2. Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan

    Tetsuhiko Tachikawa & Akemi Takahashi

  3. Department of Pathology, Saitama Medical Center, Saitama Medical University, Saitama, Japan

    Morihiro Higashi & Jun-ichi Tamaru

  4. Department of Internal Medicine, Saitama Medical Center, Saitama Medical University, Saitama, Japan

    Koji Yakabi

Authors
  1. Youichi Kumagai
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  2. Tetsuhiko Tachikawa
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Correspondence to Youichi Kumagai.

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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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Kumagai, Y., Tachikawa, T., Higashi, M. et al. Thymidine phosphorylase and angiogenesis in early stage esophageal squamous cell carcinoma. Esophagus 15, 19–26 (2018). https://doi.org/10.1007/s10388-017-0588-2

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  • DOI: https://doi.org/10.1007/s10388-017-0588-2

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