Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a chemoresistance marker in human oral squamous cell carcinoma treated with cisplatin
Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a chemoresistance marker in human oral squamous cell carcinoma treated with cisplatin
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DOI：
10.1016/s1368-8375(02)00038-6
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发表时间：
2003-02-01
期刊：
影响因子：
4.8
通讯作者：
Takebayashi, Y
中科院分区：
文献类型：
--
作者：
Miyashita, H;Nitta, Y;Takebayashi, Y
口腔鳞状细胞癌治疗中的一个重要临床问题是对基于顺铂的化疗产生的内在/获得性耐药。据报道，铜转运P型腺苷三磷酸酶（ATP7B）在体外与顺铂耐药相关（Komatsu等人，《癌症研究》60卷，1312 - 1316页，2000年）。然而，这种转运蛋白的临床意义此前尚未得到探讨。本研究的目的是调查ATP7B是否在口腔鳞状细胞癌中表达，以及其表达是否与预后以及对顺铂治疗的反应性降低相关。从70例口腔鳞状细胞癌患者的肿瘤中获取活检组织，其中51例患者接受了基于顺铂的术前化疗。我们使用抗ATP7B单克隆抗体对51例口腔鳞状细胞癌及邻近肿瘤组织进行了ATP7B的免疫组化分析。还通过对1991年至2000年期间的死亡随访数据进行生存分析，研究了ATP7B在口腔鳞状细胞癌患者预后中的意义。我们回顾性地研究了原发性口腔鳞状细胞癌中ATP7B的表达及其与化疗效果的关联。在分析的癌组织中，54.9%（28/51例）观察到肿瘤细胞有不同程度的细胞质染色。ATP7B阳性肿瘤患者对化疗的反应明显劣于ATP7B阴性肿瘤患者（P = 0.03）。接受基于顺铂化疗且肿瘤ATP7B阳性的患者总体生存率明显低于ATP7B阴性肿瘤患者（P = 0.015）。这些发现表明，口腔鳞状细胞癌中高水平的ATP7B表达与接受基于顺铂化疗的口腔鳞状细胞癌患者不良的临床结局相关。ATP7B的表达可能是某些患者选择顺铂的术前指标。（C）2002年由爱思唯尔科学有限公司出版
An important clinical problem in the treatment of oral squamous cell carcinoma is the intrinsic/acquired resistance to cisplatin-based chemotherapy. Copper-transporting P-type adenosine triphosphate (ATP7B) has been reported to be associated with cisplatin resistance in vitro (Komatsu, et al., Cancer Res 60, 1312-1316,2000). However, the clinical significance of this transporter has not previously been addressed. Our aim of this study was to investigate if ATP7B is expressed in oral squamous cell carcinoma and whether its expression correlates with prognosis and reduced responsiveness to cisplatin treatment. Biopsy tissues were obtained from the tumors of 70 patients with oral SCC, and 51 patients received cisplatin-based preoperative chemotherapy. We performed immunohistochemical analysis of ATP7B using monoclonal antibody against ATP7B in 51 oral SCC and adjacent neoplastic tissues. The significance of ATP7B in the prognosis of patients with oral SCC was also examined in the survival analysis of mortality follow-up data covering the period 1991 through 2000. We retrospectively examined the expression of ATP7B in primary oral SCC carcinoma and its association with chemotherapeutic effect. A variable degree of cytoplasmic staining of tumor cells was observed in 54.9% (28/51 cases) of the analyzed carcinomas. Patients with ATP7B-positive tumors had a significantly inferior response to chemotherapy compared with the patients with ATP7B-negative tumors (P =0.03). The patients who received cisplatin-based chemotherapy with ATP7B-positive carcinomas had a significantly poorer overall survival than those with ATP7B-negative tumors (P=0.015). These findings suggest that high levels of ATP7B expression in oral SCC are associated with unfavorable clinical outcome in patients with oral SCCs treated with cisplatin-based chemotherapy. ATP7B expression may be a preoperative indicator for a choice of cisplatin in some patients. (C) 2002 Published by Elsevier Science Ltd.