Yoshikawa T, Suzuki K, Kobayashi O, Sairenji M, Motohashi H, Tsuburaya A, Nakamura Y, Shimizu A, Yanoma S, Noguchi Y
The Third Department of Surgery, Kanagawa Cancer Center, Yokohama City University, School of Medicine, Japan.
Br J Cancer. 1999 Mar;79(7-8):1145-50. doi: 10.1038/sj.bjc.6690182.
Previous studies demonstrated that the immunohistochemical expression of thymidine phosphorylase (dThdPase) was related with distant metastasis and disease progression. In this study we investigated the production of dThdPase/platelet-derived endothelial cell growth factor in gastric cancer quantitatively. In a total of 75 tumour tissues and 60 normal gastric mucosa specimens, dThdPase protein concentrations were determined by ELISA. The amount of dThdPase was significantly higher in the tumour tissue than in the normal tissue. Intratumoural dThdPase concentrations were significantly higher in Borrmann types I and II macroscopically, in poorly differentiated and solid type histologically, in the medullary type of the tumour stroma, and in the tumour-invading serosa. In the medullary type of the amount of tumour stroma, protein levels of dThdPase were positively correlated with the vertical diameter of the tumour (r = 0.580, P = 0.019). By immunohistochemical study, dThdPase expression on tumour cells was observed in all seven specimens with high dThdPase protein levels, but not in all 14 cases with low dThdPase protein levels (P < 0.05). In summary, these data indicated that dThdPase is up-regulated in advanced solid types of gastric cancer, suggesting that dThdPase production in carcinoma cells might be induced by the microenvironment.
先前的研究表明，胸苷磷酸化酶（dThdPase）的免疫组化表达与远处转移及疾病进展相关。在本研究中，我们定量检测了胃癌中dThdPase/血小板衍生内皮细胞生长因子的产生情况。在总共75份肿瘤组织和60份正常胃黏膜标本中，采用酶联免疫吸附测定法（ELISA）测定dThdPase蛋白浓度。肿瘤组织中dThdPase的含量显著高于正常组织。在Borrmann I型和II型（大体分型）、低分化和实体型（组织学类型）、肿瘤间质的髓质型以及侵犯浆膜的肿瘤中，瘤内dThdPase浓度显著更高。在肿瘤间质的髓质型中，dThdPase的蛋白水平与肿瘤的垂直直径呈正相关（r = 0.580，P = 0.019）。通过免疫组化研究，在所有7份dThdPase蛋白水平高的标本中均观察到肿瘤细胞上有dThdPase表达，但在所有14份dThdPase蛋白水平低的病例中并非都有表达（P < 0.05）。总之，这些数据表明dThdPase在进展期实体型胃癌中上调，提示癌细胞中dThdPase的产生可能由微环境诱导。
