Takebayashi Y, Natsugoe S, Baba M, Akiba S, Fukumoto T, Miyadera K, Yamada Y, Takao S, Akiyama S, Aikou T
First Department of Surgery, Faculty of Medicine, Kagoshima University, Japan.
Cancer. 1999 Jan 15;85(2):282-9. doi: 10.1002/(sici)1097-0142(19990115)85:2<282::aid-cncr3>3.0.co;2-t.
Experimental evidence has shown that thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and has angiogenic activity. The enzymatic activity of dThdPase was needed for the angiogenesis by the enzyme. These observations were catalysts for the current study.
The authors examined retrospectively the expression of the angiogenic factor dThdPase in 163 primary esophageal squamous cell carcinomas and its association with angiogenesis and clinicopathologic findings. To determine whether dThdPase expression was a prognostic factor after adjustment for the established prognostic factors and microvessel count, the authors conducted a survival analysis using the Cox proportional hazards model.
dThdPase was expressed significantly more frequently (P < 0.001) in esophageal carcinomas (83 of 163, 50.9%) than in adjacent nonneoplastic esophageal tissue samples (20 of 163, 12.3%). Microvessel counts were significantly higher (P < 0.001) in dThdPase positive carcinomas (18.3+/-6.2) than in dThdPase negative carcinomas (8.2+/-7.5). Significant correlations were observed between dThdPase expression and numerous clinicopathologic findings, including pT, pN, pM categories; lymphatic invasion; venous invasion; and residual tumors. Prognostic variables studied using a Cox hazard regression model confirmed that dThdPase expression was an independent prognostic factor in esophageal squamous cell carcinoma, although pN category was the best predictor of patient survival.
This study indicated that in esophageal squamous cell carcinoma, dThdPase expression is associated with angiogenesis and is an unfavorable prognostic factor. These findings implied that the inhibition of dThdPase would improve the prognoses of some patients with dThdPase positive esophageal tumors.
实验证据表明,胸苷磷酸化酶(dThdPase)与血小板衍生的内皮细胞生长因子(PD - ECGF)相同,且具有血管生成活性。该酶的血管生成作用需要dThdPase的酶活性。这些观察结果促成了本研究。
作者回顾性研究了163例原发性食管鳞状细胞癌中血管生成因子dThdPase的表达情况及其与血管生成和临床病理特征的关系。为了确定在调整既定预后因素和微血管计数后dThdPase表达是否为预后因素,作者使用Cox比例风险模型进行了生存分析。
食管癌(163例中的83例,50.9%)中dThdPase的表达频率显著高于相邻的非肿瘤性食管组织样本(163例中的20例,12.3%)(P < 0.001)。dThdPase阳性的癌组织中微血管计数(18.3±6.2)显著高于dThdPase阴性的癌组织(8.2±7.5)(P < 0.001)。观察到dThdPase表达与许多临床病理特征之间存在显著相关性,包括pT、pN、pM分期;淋巴浸润;静脉浸润;以及残留肿瘤。使用Cox风险回归模型研究的预后变量证实,dThdPase表达是食管鳞状细胞癌的独立预后因素,尽管pN分期是患者生存的最佳预测指标。
本研究表明,在食管鳞状细胞癌中,dThdPase表达与血管生成相关,是一个不良预后因素。这些发现意味着抑制dThdPase可能会改善一些dThdPase阳性食管肿瘤患者的预后。