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Angiogenic factor thymidine phosphorylase associates with angiogenesis and lymphangiogenesis in the intestinal-type gastric cancer

Zhang, Xianglan1,2; Zheng, Zhenlong3; Shin, You Keun4; Kim, Ki-Yeol1; Rha, Sun Young4,5; Noh, Sung Hoon6; Chung, Hyun Cheol4,5; Jeung, Hei-Cheul4,5,7

doi: 10.1097/PAT.0000000000000094
Anatomical Pathology

Summary: As an angiogenic factor, thymidine phosphorylase (TP) expression in primary tumours has been thought to be a risk factor for lymph node (LN) and hepatic metastasis in patients with gastric adenocarcinoma. However, the molecular basis for the induction of metastasis by TP is largely unknown. We aim to elucidate the role of TP expression in gastric cancer neovascularisation and LN metastasis.

The angiogenic and lymphangiogenic activity (CD31, D2-40, Ki-67, VEGFC, VEGFR3) and expression status of TP were detected in 103 resected human gastric carcinoma samples by immunohistochemistry. The influence of TP expression on neovascularisation and cancer cell invasion was further comparatively investigated in two groups of nude mice intraperitoneally injected with TP overexpressing MKN-45 cells (MKN-45/TP) and control cells (MKN-45/CV).

In gastric cancer tissues, we found that high TP expression and various angiogenic and lymphangiogenic activities were significantly associated with poor prognostic outcomes. In addition, TP expression was also found to be associated with neovascularisation activity of gastric cancer tissues. In vivo, the MKN-45/TP group exhibited significantly increased infiltrating tumour nodules and neovascularisation activity compared to the MKN-45/CV group.

TP could strongly influence gastric cancer progression via the dual activities of angiogenesis and lymphangiogenesis.

1Department of Pathology, Yanbian University Hospital, Yanji City, Jilin Province, China

2Oral Cancer Research Institute, College of Dentistry, Yonsei University, Seoul, South Korea

3Department of Dermatology, Yanbian University Hospital, Yanji City, Jilin Province, China

4Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul

5Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul

6Department of Surgery, Yonsei University College of Medicine, Seoul

7Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea

Address for correspondence: Professor H-C. Jeung, Division of Medical Oncology, Department of Internal Medicine, Gangnam Severance Hospital, Cancer Metastasis Research Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, 120-752, Korea. E-mail: jeunghc1123@yuhs.ac

Received 18 July, 2013

Revised 28 November, 2013

Accepted 2 December, 2013

© 2014 Royal College of Pathologists of Australasia
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