Koizumi W, Saigenji K, Nakamaru N, Okayasu I, Kurihara M
Department of Gastroenterology, East Hospital, Kitasato University, School of Medicine, Sagamihara City, Kanagawa, Japan.
Oncology. 1999 Apr;56(3):215-22. doi: 10.1159/000011968.
No reliable method is available for predicting the response to chemotherapy in patients with gastric cancer. The anticancer drug 5'-deoxy-5-fluorouridine (5'-DFUR) is converted into 5-fluorouracil (5-FU) by thymidine phosphorylase (dThdPase). We studied the relation between the expression of dThdPase in tumor tissue and the response to treatment with 5'-DFUR to determine if this enzyme can be used to predict the response to chemotherapy.
We performed endoscopic biopsy and studied the expression of dThdPase by immunostaining with anti-dThdPase monoclonal antibody in 41 patients with inoperable advanced gastric carcinomas before they received multiple-drug chemotherapy, including 5'-DFUR. The relation between the expression of dThdPase and the response to chemotherapy was studied. We also studied the characteristics of positive cells against anti-dThdPase monoclonal antibody.
The response rate among patients whose tumors were positive for dThdPase expression (56.8%, 21/37) was higher than that among patients whose tumors were negative for dThdPase expression (0%, 0/4; p = 0.048). Spindle-shaped cells darkly expressing dThdPase were sporadically seen surrounding cancer nests in some patients. Multiple-antibody immunostaining suggested that these spindle-shaped cells were perivascular mesenchymal cells. The response rate was 82.4% (14/17) among patients with spindle-shaped cells strongly positive for dThdPase, as compared with 29.2% (7/24) among those with spindle-shaped cells weakly positive or negative for dThdPase (p = 0.00131). The expression of spindle-shaped cells darkly stained with dThdPase was the factor most strongly related to the response to chemotherapy (odds ratio = 35.513, p = 0.0027).
The expression of dThdPase in stromal spindle-shaped cells may be a useful index in predicting the response to 5'-DFUR in patients with gastric cancer.
目前尚无可靠方法预测胃癌患者对化疗的反应。抗癌药物5'-脱氧-5-氟尿苷（5'-DFUR）可被胸苷磷酸化酶（dThdPase）转化为5-氟尿嘧啶（5-FU）。我们研究了肿瘤组织中dThdPase的表达与5'-DFUR治疗反应之间的关系，以确定该酶是否可用于预测化疗反应。
我们对41例无法手术的晚期胃癌患者进行了内镜活检，并用抗dThdPase单克隆抗体免疫染色研究dThdPase的表达，这些患者在接受包括5'-DFUR在内的多药化疗之前。研究了dThdPase的表达与化疗反应之间的关系。我们还研究了抗dThdPase单克隆抗体阳性细胞的特征。
dThdPase表达阳性的患者的反应率（56.8%，21/37）高于dThdPase表达阴性的患者（0%，0/4；p = 0.048）。在一些患者中，偶尔可见在癌巢周围有深色表达dThdPase的梭形细胞。多抗体免疫染色表明这些梭形细胞是血管周围间充质细胞。dThdPase强阳性的梭形细胞患者的反应率为82.4%（14/17），而dThdPase弱阳性或阴性的梭形细胞患者的反应率为29.2%（7/24）（p = 0.
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