The Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
Clin Cancer Res. 2011 Apr 15;17(8):2561-9. doi: 10.1158/1078-0432.CCR-10-1963. Epub 2010 Dec 21.
Chemoradiation therapy (CRT) is now widely recognized as bladder-preserving therapy for muscle-invasive bladder cancer (MIBC). However, some patients who fail CRT may miss the chance to be cured by cystectomy. Therefore, it is important to select patients with MIBC who are expected to have a good response to CRT. Several reports indicate that the excision repair cross-complementing group 1 (ERCC1) gene is associated with resistance to cisplatin and radiation therapy. In this study, we examined the correlation between ERCC1 and CRT in vitro and in vivo in bladder cancer.
Bladder cancer cell lines T24, 5637, Cl8-2 (multidrug-resistant subline of T24), and CDDP10-3 (cisplatin-resistant subline of T24) were used for in vitro assays to measure ERCC1 expression level and growth inhibition with cisplatin or ionizing radiation (IR). We then examined by immunohistochemistry that whether ERCC1 nuclear staining correlates with the efficacy of CRT using cisplatin in 22 patients with MIBC.
Cl8-2 cells expressed ERCC1 mRNA 5.96-fold higher than did T24. Cl8-2 and CDDP10-3 were more resistant to cisplatin or IR than was T24. Resistance to IR, but not to cisplatin, was removed by suppressing ERCC1 using siRNA in both Cl8-2 and CDDP10-3 cells. In immunohistochemistry with ERCC1, 6 of 8 positive cases did not have complete response to CRT, whereas 12 of 14 negative cases had complete response. Sensitivity and specificity were 75% and 85.7%, respectively (P = 0.008).
Although further study is needed, ERCC1 expression level may predict the efficacy of CRT for MIBC.
化学放射疗法（CRT）目前被广泛认为是肌层浸润性膀胱癌（MIBC）的保膀胱治疗方法。然而，一些 CRT 失败的患者可能会错过根治性膀胱切除术的治愈机会。因此，选择预计对 CRT 有良好反应的 MIBC 患者非常重要。有几项报告表明，切除修复交叉互补基因 1（ERCC1）与顺铂和放射治疗的耐药性有关。在这项研究中，我们研究了膀胱癌中 ERCC1 与 CRT 的体外和体内相关性。
我们使用膀胱癌细胞系 T24、5637、Cl8-2（T24 的多药耐药亚系）和 CDDP10-3（T24 的顺铂耐药亚系）进行体外实验，以测量 ERCC1 表达水平，并分别用顺铂或电离辐射（IR）抑制细胞生长。然后，我们通过免疫组织化学检测 22 例 MIBC 患者中 ERCC1 核染色与 CRT 中顺铂疗效的相关性。
Cl8-2 细胞的 ERCC1 mRNA 表达水平比 T24 高 5.96 倍。Cl8-2 和 CDDP10-3 对顺铂或 IR 的耐药性均高于 T24。在 Cl8-2 和 CDDP10-3 细胞中，用 siRNA 抑制 ERCC1 可消除对 IR 的耐药性，但对顺铂的耐药性没有消除。在 ERCC1 的免疫组化中，8 例阳性病例中有 6 例对 CRT 无完全缓解，而 14 例阴性病例中有 12 例有完全缓解。敏感性和特异性分别为 75%和 85.7%（P = 0.008）。
尽管需要进一步研究，但 ERCC1 表达水平可能预测 MIBC 的 CRT 疗效。
