Hsu Chih-Hung, Chen Chi-Long, Hong Ruey-Long, Chen Kai-Lii, Lin Jing-Fan, Cheng Ann-Lii
Department of Oncology, National Taiwan University Hospital, Taipei, ROC.
Oncology. 2002;62(4):305-12. doi: 10.1159/000065061.
Nasopharyngeal carcinoma (NPC) is one of the dominant cancers in South China and Taiwan. Although NPC is highly chemosensitive, the use of chemotherapy for treating patients with recurrent or metastatic NPC has not been very successful. The emergence of drug resistance may be one of the major reasons. However, the mechanisms of drug resistance of NPC have never been addressed before. In this study, we sought to clarify the role of classical drug resistance markers in predicting the chemosensitivity and the prognosis of patients with advanced NPC.
In a cohort of 202 consecutive patients diagnosed at the Department of Pathology of the National Taiwan University Hospital, 44 patients with adequately preserved pretreatment tumor tissues and complete clinical information regarding the details of chemotherapy and tumor response were identified. The expression of multidrug resistance (MDR1), glutathione-S-transferase-pi (GSTpi), and p53 were determined by immunohistochemistry. Tumor response to chemotherapy and survival of the patients were the endpoints of this analysis.
Thirty-four patients received cisplatin-based regimens, and 28 of them were enrolled in a prospective trial using a doxorubicin-containing regimen. The overall response rate was 70%. Expression of MDR1 was seen in only 5 cases (11%) and was associated with a significantly worse overall survival, yet did not appear to predict chemoresistance to the doxorubicin-containing regimen. Overexpression of p53 was seen in 22 patients, and surprisingly, was correlated with chemoresponse and a trend towards better survival. GSTpi expression was demonstrated in 13 cases (30%) and was not correlated with chemoresistance to cisplatin-containing regimens and overall survival.
In this relatively small cohort, positive MDR1 immunostaining predicted a poor overall survival for recurrent or metastatic NPC patients receiving chemotherapy. Overexpression of p53 by immunohistochemical staining, however, was associated with a better response rate to systemic chemotherapy and a trend towards better survival.
鼻咽癌（NPC）是中国南方和台湾地区的主要癌症之一。尽管鼻咽癌对化疗高度敏感，但用于治疗复发或转移性鼻咽癌患者的化疗效果并不十分理想。耐药性的出现可能是主要原因之一。然而，鼻咽癌的耐药机制此前从未得到探讨。在本研究中，我们试图阐明经典耐药标志物在预测晚期鼻咽癌患者化疗敏感性和预后中的作用。
在国立台湾大学医院病理科连续诊断的202例患者队列中，确定了44例预处理肿瘤组织保存完好且有关于化疗细节和肿瘤反应的完整临床信息的患者。通过免疫组织化学测定多药耐药（MDR1）、谷胱甘肽-S-转移酶-pi（GSTpi）和p53的表达。本分析的终点是患者对化疗的反应和生存情况。
34例患者接受了以顺铂为基础的方案，其中28例参加了使用含阿霉素方案的前瞻性试验。总缓解率为70%。仅5例（11%）出现MDR1表达，且与总体生存率显著较差相关，但似乎不能预测对含阿霉素方案的化疗耐药性。22例患者出现p53过表达，令人惊讶的是，其与化疗反应及生存改善趋势相关。13例（30%）出现GSTpi表达，且与对含顺铂方案的化疗耐药性及总体生存率无关。
在这个相对较小的队列中，MDR1免疫染色阳性预测接受化疗的复发或转移性鼻咽癌患者总体生存率较差。然而，通过免疫组织化学染色检测到的p53过表达与全身化疗的较好反应率及生存改善趋势相关。
