Department of Oncology, University of Calgary, Calgary, AB, Canada.
Int J Radiat Oncol Biol Phys. 2013 Mar 1;85(3):721-7. doi: 10.1016/j.ijrobp.2012.06.021. Epub 2012 Jul 24.
ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters.
A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years.
The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067).
In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on multivariate analysis.
在许多肿瘤部位，ERCC1（切除修复交叉互补组 1）的表达已被证明是顺铂耐药的分子标志物，但在宫颈癌患者中尚未得到很好的研究。本研究的目的是在一个大型多中心队列中测量接受放化疗治疗的局部晚期宫颈癌患者的肿瘤 ERCC1，并将其表达与临床结局参数相关联。
共评估了来自 3 个加拿大主要癌症中心的 264 例接受根治性放化疗的局部晚期宫颈癌患者。提取预处理的福尔马林固定、石蜡包埋的肿瘤标本，并构建组织微阵列。使用 AQUA（R）技术测量肿瘤 ERCC1（FL297 抗体）。进行统计学分析，以确定临床因素和 ERCC1 状态与无进展生存期（PFS）和 5 年总生存期（OS）的相关性。
大多数患者为国际妇产科联合会（FIGO）分期 II 期疾病（n=119，45%）；中位肿瘤大小为 5cm。OS 与肿瘤大小（HR 1.16，P=.018）、预处理血红蛋白状态（HR 2.33，P=.00027）和 FIGO 分期相关。此外，肿瘤 ERCC1 状态（核-细胞质比）与 PFS（HR 2.33 [1.05-5.18]，P=.038）和 OS（HR 3.13 [1.27-7.71]，P=.013）相关。当模型调整为临床因素时，ERCC1 状态在多变量分析中并不显著：对于 PFS（HR 1.49 [0.61-3.6]，P=.38）；对于 OS（HR 2.42 [0.94-6.24]，P=.067）。
在接受根治性放化疗的局部晚期宫颈癌患者的这个大型多中心队列中，分期、肿瘤大小和预处理血红蛋白状态与 PFS 和 OS 显著相关。在这些患者的单变量分析中，ERCC1 状态似乎具有预后影响，但在多变量分析中与结局无关。
