Miyashita Hitoshi, Nitta Yasutaka, Mori Shiro, Kanzaki Atsuko, Nakayama Kentaro, Terada Kunihiko, Sugiyama Toshihiro, Kawamura Hiroshi, Sato Atsushi, Morikawa Hidehiro, Motegi Katutoshi, Takebayashi Yuji
Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, Aobaku, Seiryomachi 4-1, Sendai 980-8575, Japan.
Oral Oncol. 2003 Feb;39(2):157-62. doi: 10.1016/s1368-8375(02)00038-6.
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.
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存在内在/获得性耐药。据报道，铜转运P型三磷酸腺苷酶（ATP7B）在体外与顺铂耐药有关（小松等人，《癌症研究》60，1312 - 1316，2000）。然而，此前尚未探讨该转运蛋白的临床意义。本研究的目的是调查ATP7B在口腔鳞状细胞癌中是否表达，以及其表达是否与预后和对顺铂治疗反应性降低相关。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相邻肿瘤组织进行了ATP7B的免疫组化分析。在对1991年至2000年期间死亡率随访数据的生存分析中，还研究了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54.9%（28/51例）的分析癌组织中观察到肿瘤细胞有不同程度的细胞质染色。与ATP7B阴性肿瘤患者相比，ATP7B阳性肿瘤患者对化疗的反应明显较差（P = 0.03）。接受基于顺铂化疗且癌组织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临床结局相关。ATP7B表达可能是某些患者选择顺铂治疗的术前指标。
