Peltola Katriina Johanna, Penttilä Patrick, Rautiola Juhana, Joensuu Heikki, Hänninen Erkki, Ristimäki Ari, Bono Petri
Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland.
Pathology, Research Programs Unit and HUSLAB, University of Helsinki, Helsinki, Finland.
Clin Genitourin Cancer. 2017 Aug;15(4):487-494. doi: 10.1016/j.clgc.2017.01.021. Epub 2017 Feb 1.
Treatment of patients with metastatic renal cell carcinoma (mRCC) has improved substantially since the introduction of targeted therapies, but no predictive biomarkers are available. The proto-oncogene c-Met is involved in tumor angiogenesis, development, and metastasis. The main objective was to evaluate c-Met expression in sunitinib-treated patients with mRCC, including patients with bone metastases.
c-Met expression was analyzed from 137 formalin-fixed paraffin-embedded tumor samples using a validated immunostaining protocol.
Patients with low c-Met expression (n = 78) had longer progression-free survival (PFS) (median 14.3 vs. 6.5 months; P < .001) and overall survival (OS) (median 32.1 vs. 20.1 months; P = .049) than those with high expression. High c-Met expression was an independent predictor of unfavorable PFS in a Cox proportional hazards model adjusted for the Heng risk criteria (HR 1.60 [1.09-2.35]; P = .016). In a subgroup of patients with no bone metastases (n = 106), low c-Met expression was associated with a both longer OS (unadjusted HR 0.63 [95% CI, 0.42-0.95]; P = .034) and PFS (unadjusted HR 0.47 [95% CI, 0.31-0.71]; P < .001).
High c-Met expression was associated with poor survival in patients with mRCC treated with sunitinib. Interestingly, the prognostic role may vary based on the location of metastases.
自引入靶向治疗以来,转移性肾细胞癌(mRCC)患者的治疗有了显著改善,但尚无预测性生物标志物。原癌基因c-Met参与肿瘤血管生成、发展和转移。主要目的是评估舒尼替尼治疗的mRCC患者(包括骨转移患者)中c-Met的表达情况。
使用经过验证的免疫染色方案,对137份福尔马林固定石蜡包埋的肿瘤样本进行c-Met表达分析。
c-Met低表达患者(n = 78)的无进展生存期(PFS)更长(中位时间14.3个月对6.5个月;P <.001),总生存期(OS)也更长(中位时间32.1个月对20.1个月;P =.049)。在根据恒氏风险标准调整的Cox比例风险模型中,c-Met高表达是不良PFS的独立预测因素(风险比[HR] 1.60 [1.09 - 2.35];P =.016)。在无骨转移患者亚组(n = 106)中,c-Met低表达与更长的OS(未调整HR 0.63 [95%置信区间,0.42 - 0.95];P =.034)和PFS(未调整HR 0.47 [95%置信区间,0.31 - 0.71];P <.001)相关。
舒尼替尼治疗的mRCC患者中,c-Met高表达与较差的生存率相关。有趣的是,预后作用可能因转移部位而异。