The expression of thymidine phosphorylase and its correlation with angiogenesis in gastric adenocarcinoma.
BACKGROUND
It has been recently reported that thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF). dThdPase is known to be one of the angiogenic factors. Expression of dThdPase has been detected both in cancer cells and in stroma cells. However, the role of dThdPase, in cancer cells and in stroma cells regarding, neovascularization in gastric adenocarcinoma is still unclear. In this study, we analyzed the correlation between dThdPase activity and neovascularization in gastric cancer.


METHODS
We obtained fresh samples (tumors and adjacent normal mucosas) from 67 patients with gastric cancer who underwent gastrectomy between 1993 and 1994. The dThdPase activity was analyzed by the ELISA (enzyme-linked immunosorbent assay) method and by the immunohistochemical staining. Microvessel density (MVD) and vascular endothelial growth factor expression of tumors were analyzed by immunohistochemical staining.


RESULTS
The dThdPase activity of tumors (117 +/- 98 U/mg protein) was significantly higher than that of normal mucosas (46 +/- 36 U/mg protein, P < 0.0001). The expression of dThdPase was detected by immunostaining in stroma cells but not in mucosal cells in normal tissues. Based on the immunostaining results, 16 tumors expressed dThdPase both in cancer cells and stroma cells. The mean dThdPase activity and the mean MVD of these 16 tumors were significantly higher than those of 15 tumors with expression of dThdPase only in the stroma cells, and than those of 36 tumors with expression of dThdPase in neither the cancer cells or the stroma cells. The MVD of tumors strongly correlated with the dThdPase activity of tumors detected by the ELISA method (P < 0.0001).


CONCLUSIONS
The total amount of dThdPase produced by cancer cells and stroma cells may influence tumor angiogenesis in gastric cancer.
Ikeguchi
M
M
Department of Surgery I, Faculty of Medicine, Tottori University, Yonago, Japan.
Oka
S
S
Saito
H
H
Kondo
A
A
Tsujitani
S
S
Maeta
M
M
Kaibara
N
N
D000230:Adenocarcinoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D016228:Endothelial Growth Factors / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000201:enzymology / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000201:enzymology* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D013939:Thymidine Phosphorylase / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013939:Thymidine Phosphorylase