Volm M, Mattern J
German Cancer Research Center, Heidelberg.
Anticancer Res. 1992 Nov-Dec;12(6B):2293-6.
Human non-small cell lung carcinomas of previously untreated patients were analyzed for expression of thymidylate synthase (TS) using immunohistochemistry. Of the 94 tumors, 67 were positive for TS and 27 negative. A significant correlation between the expression of TS and the resistance to doxorubicin was found (p < 0.0001). Eighty-four percent of the TS-positive tumors were resistant to doxorubicin, whereas of the 27 TS-negative tumors only 44 percent were resistant. A group of patients (n = 13) were treated with combination chemotherapy including 5-fluorouracil, doxorubicin and cisplatinum. Seven of the 8 tumors which were TS-positive were clinically progressive, whereas 4 of 5 tumors which were TS-negative showed clinical remission after chemotherapy (p < 0.05; Fisher exact test). The patients whose tumors were TS negative lived significantly longer than those with TS-positive tumors. The median survival times were 185 weeks for patients with TS-negative and 41 weeks for patients with TS-positive tumors (p < 0.05; log-rank-test). Thus the expression of TS is a strong prognostic factor for resistance of tumors, clinical course and survival of patients with non-small cell lung carcinomas.
采用免疫组织化学方法分析了未经治疗的人类非小细胞肺癌患者肿瘤组织中胸苷酸合成酶（TS）的表达情况。在94例肿瘤组织中，67例TS表达阳性，27例表达阴性。结果发现TS表达与对阿霉素的耐药性之间存在显著相关性（p < 0.0001）。TS阳性肿瘤中有84%对阿霉素耐药，而27例TS阴性肿瘤中仅有44%耐药。一组患者（n = 13）接受了包含5-氟尿嘧啶、阿霉素和顺铂的联合化疗。8例TS阳性肿瘤患者中有7例临床病情进展，而5例TS阴性肿瘤患者中有4例化疗后临床缓解（p < 0.05；Fisher精确检验）。肿瘤TS阴性的患者生存时间显著长于TS阳性患者。TS阴性患者的中位生存时间为185周，TS阳性患者为41周（p < 0.05；对数秩检验）。因此，TS的表达是影响非小细胞肺癌患者肿瘤耐药性、临床病程及生存的一个重要预后因素。
