Sitnikova Lioudmila, Mendese Gary, Liu Qin, Woda Bruce A, Lu Di, Dresser Karen, Mohanty Sambit, Rock Kenneth L, Jiang Zhong
Department of Urology, University of Massachusetts Medical Center, Worcester, Massachusetts 01605, USA.
Clin Cancer Res. 2008 Mar 15;14(6):1701-6. doi: 10.1158/1078-0432.CCR-07-2039.
In this study, we investigated whether an oncofetal protein, IMP3, can serve as a new biomarker to predict progression and metastasis of early-stage urothelial carcinoma of the bladder.
The expression of IMP3 in 242 patients with primary superficial bladder urothelial carcinoma and metastatic urothelial carcinoma was evaluated by immunohistochemistry. Patients with primary superficial urothelial carcinoma of the bladder were further investigated by use of survival analysis.
Twenty percent (42 of 214) of primary superficial urothelial carcinomas and 93% (26 of 28) of metastatic urothelial carcinomas expressed IMP3. Kaplan-Meier plots and log-rank tests showed that patients with IMP3-positive tumors had a much lower progression-free survival (P = 0.0002) and disease-free survival rate (P = 0.0067) than did those with IMP3-negative tumors. The 5-year progression-free and disease-free survival rates were 91% and 94% in IMP3-negative patients versus 64% and 76% in IMP3-positive patients, respectively. Sixty percent of IMP3-positive patients with superficial invasive urothelial carcinoma at initial diagnosis went on to develop metastases, whereas no metastasis was found in IMP3-negative patients (P = 0.0017). In the multivariable Cox analysis, patients with IMP3 expression in their superficial urothelial carcinomas subsequently developed invasive tumors or metastasis at a rate that was about five times greater than cases without expression of IMP3 adjusting for other well-known clinical variables (tumor stage and grade, etc.).
Our findings indicate that IMP3 is an independent prognostic marker that can identify a group of patients with a high potential to develop progression and who might benefit from early aggressive therapy.
在本研究中,我们调查了一种癌胚蛋白IMP3是否可作为预测早期膀胱尿路上皮癌进展和转移的新型生物标志物。
采用免疫组织化学方法评估242例原发性浅表性膀胱尿路上皮癌和转移性尿路上皮癌患者中IMP3的表达情况。对原发性浅表性膀胱尿路上皮癌患者进一步进行生存分析。
214例原发性浅表性尿路上皮癌中有20%(42例)表达IMP3,28例转移性尿路上皮癌中有93%(26例)表达IMP3。Kaplan-Meier曲线和对数秩检验显示,IMP3阳性肿瘤患者的无进展生存期(P = 0.0002)和无病生存率(P = 0.0067)远低于IMP3阴性肿瘤患者。IMP3阴性患者的5年无进展生存率和无病生存率分别为91%和94%,而IMP3阳性患者分别为64%和76%。初始诊断为浅表浸润性尿路上皮癌的IMP3阳性患者中有60%发生转移,而IMP3阴性患者未发现转移(P = 0.0017)。在多变量Cox分析中,浅表性尿路上皮癌中表达IMP3的患者随后发生浸润性肿瘤或转移的几率比未表达IMP3的患者高约五倍,其他已知临床变量(肿瘤分期和分级等)已进行校正。
我们的研究结果表明,IMP3是一种独立的预后标志物,可识别出一组具有高进展潜力且可能从早期积极治疗中获益的患者。