胸苷酸合成酶而非切除修复交叉互补组 1 肿瘤表达可预测培美曲塞为基础化疗治疗的恶性胸膜间皮瘤患者的结局。

Thymidylate synthase but not excision repair cross-complementation group 1 tumor expression predicts outcome in patients with malignant pleural mesothelioma treated with pemetrexed-based chemotherapy.

机构信息

University of Torino, Division of Pathology, Thoracic Oncology, and Thoracic Surgery, Department of Clinical and Biological Sciences at San Luigi Hospital, Orbassano, Italy.

出版信息

J Clin Oncol. 2010 Mar 20;28(9):1534-9. doi: 10.1200/JCO.2009.25.9275. Epub 2010 Feb 22.

DOI:10.1200/JCO.2009.25.9275

PMID:20177021

Abstract

PURPOSE

The relationship between thymidylate synthase (TS) expression and outcome in patients with malignant pleural mesothelioma (MPM) treated with pemetrexed (P) was retrospectively evaluated.

PATIENTS AND METHODS

Sixty histologically confirmed patients with MPM previously treated with P and platinum (45 of 60) or as single agent (15 of 60) were retrospectively considered. Eighty-one control patients with MPM not P-treated were also evaluated. TS and excision repair cross-complementation group 1 (ERCC1) gene expression levels were evaluated by real-time polymerase chain reaction and by immunohistochemistry using the H-score.

RESULTS

Median TS H-score value was 90 (range, 5 to 240). A significant correlation between low TS protein expression and longer time to progression (TTP; 17.9 v 7.9 months; hazard ratio [HR], 2.05, 95% CI, 1.19 to 3.77; P = .02) or overall survival (OS; 30 v 16.7 months; HR, 2.38; 95% CI, 1.15 to 4.91; P = .019) was found when patients were divided according to median H-score. Conversely, TS mRNA levels were not significantly correlated with outcome. In platinum-treated patients (n = 45), no correlation was found with survival according to ERCC1 median H-score, but patients in the lower tertile had a significantly shorter survival (HR, 3.06; 95% CI, 1.08 to 8.69; P = .035). In control MPMs, TS had no prognostic role. At multivariate analysis, TS protein levels were the only independent prognostic factor for both TTP (HR, 2.71; 95% CI, 1.13 to 6.49; P = .02) and OS (HR, 6.91; 95% CI, 1.90 to 25.07; P = .003).

CONCLUSION

In patients with MPM treated with P-based chemotherapy, low TS protein levels are predictive of improved TTP and OS. The role of TS assessment is worth of prospective validation in future studies on MPM.

摘要

目的

回顾性评估胸苷酸合成酶（TS）表达与培美曲塞（P）治疗恶性胸膜间皮瘤（MPM）患者结局的关系。

方法

回顾性分析 60 例经组织学证实的先前接受 P 和铂（60 例中的 45 例）或单药治疗（60 例中的 15 例）的 MPM 患者。还评估了 81 例未接受 P 治疗的对照 MPM 患者。采用实时聚合酶链反应和免疫组织化学法（H 评分）检测 TS 和切除修复交叉互补组 1（ERCC1）基因表达水平。

结果

中位 TS H 评分值为 90（范围，5 至 240）。根据中位 H 评分将患者分为两组，低 TS 蛋白表达与进展时间（TTP；17.9 与 7.9 个月；风险比[HR]，2.05，95%置信区间，1.19 至 3.77；P =.02）或总生存期（OS；30 与 16.7 个月；HR，2.38；95%置信区间，1.15 至 4.91；P =.019）显著相关。相反，根据 TS mRNA 水平与结局无显著相关性。在接受铂类治疗的患者（n = 45）中，根据 ERCC1 中位 H 评分，与生存无相关性，但处于较低三分位的患者生存时间显著缩短（HR，3.06；95%置信区间，1.08 至 8.69；P =.035）。在对照性 MPM 中，TS 无预后作用。多因素分析显示，TS 蛋白水平是 TTP（HR，2.71；95%置信区间，1.13 至 6.49；P =.02）和 OS（HR，6.91；95%置信区间，1.90 至 25.07；P =.003）的唯一独立预后因素。