Kim Min Kyoung, Cho Kyung-Ja, Kwon Gui Young, Park Seung-Il, Kim Yong Hee, Kim Jong Hoon, Song Ho-Young, Shin Ji Hoon, Jung Hwoon Yong, Lee Gin Hyug, Choi Kee Don, Kim Sung-Bae
Division of Oncology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Clin Cancer Res. 2008 Jul 1;14(13):4225-31. doi: 10.1158/1078-0432.CCR-07-4848.
To assess the significance of excision repair cross-complementation group 1 (ERCC1) expression as a predictive marker, we analyzed the effects of preoperative chemoradiotherapy on survival relative to ERCC1 status in patients with locally advanced operable esophageal cancer.
Paraffin-embedded pretreatment tumor specimens, collected by endoscopic biopsy from patients treated with surgery alone or with preoperative chemoradiotherapy followed by surgery, were immunohistochemically assayed for ERCC1 expression.
Of the 175 patients, 152 biopsy specimens were available for immunohistochemical analysis. Based on a median ERCC1 expression score of 1, we divided the samples into ERCC1-positive (score >1; 71 patients, 47%) and ERCC1-negative (score </=1; 81 patients, 53%) groups. No differences in patient and disease characteristics were observed between the two groups. However, among patients with ERCC1-negative tumors, those who received preoperative chemoradiotherapy had longer overall survival (OS) and event-free survival (EFS) than those treated with esophagectomy alone (median OS, 59.2 versus 25.4 months, P = 0.057; median EFS, 50.7 versus 19.7 months, P = 0.042). This difference was not observed among patients with ERCC1-positive tumors. In multivariate analysis, treatment modality was the major determinant of both EFS (P = 0.006) and OS (P = 0.008) for patients with ERCC1-negative tumors, whereas Eastern Cooperative Oncology Group performance status was the only significant predictor of outcome among ERCC1-positive patients. Among patients who received esophagectomy alone, those with ERCC1-positive tumors had a tendency toward longer OS and EFS (P = 0.085 and 0.094, respectively).
Patients with ERCC1-negative operable esophageal tumors show a greater benefit from preoperative chemoradiotherapy followed by esophagectomy than those who undergo esophagectomy alone.
为评估切除修复交叉互补组1（ERCC1）表达作为预测标志物的意义，我们分析了术前放化疗对局部晚期可手术食管癌患者生存的影响，并将其与ERCC1状态相关联。
通过内镜活检收集仅接受手术治疗或接受术前放化疗后再手术治疗患者的石蜡包埋预处理肿瘤标本，采用免疫组织化学方法检测ERCC1表达。
175例患者中，152份活检标本可用于免疫组织化学分析。基于ERCC1表达评分中位数为1，我们将样本分为ERCC1阳性（评分>1；71例患者，47%）和ERCC1阴性（评分≤1；81例患者，53%）两组。两组患者及疾病特征未见差异。然而，在ERCC1阴性肿瘤患者中，接受术前放化疗的患者总生存期（OS）和无事件生存期（EFS）长于单纯接受食管切除术的患者（中位OS，59.2个月对25.4个月，P = 0.057；中位EFS，50.7个月对19.7个月，P = 0.042）。ERCC1阳性肿瘤患者中未观察到这种差异。多因素分析显示，治疗方式是ERCC1阴性肿瘤患者EFS（P = 0.006）和OS（P = 0.008）的主要决定因素，而东部肿瘤协作组体能状态是ERCC1阳性患者结局的唯一显著预测因素。在仅接受食管切除术的患者中，ERCC1阳性肿瘤患者的OS和EFS有延长趋势（分别为P = 0.085和0.094）。
ERCC1阴性可手术食管癌患者接受术前放化疗后再行食管切除术比单纯接受食管切除术获益更大。
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