Clear Cell Renal Cell Carcinoma Subtypes Identified by BAP1 and PBRM1 Expression.
Clear Cell Renal Cell Carcinoma Subtypes Identified by BAP1 and PBRM1 Expression.
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通过BAP1和PBRM1表达鉴定的透明细胞肾细胞癌亚型。
DOI：
10.1016/j.juro.2015.07.113
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发表时间：
2016-01
期刊：
影响因子：
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通讯作者：
Brugarolas J
中科院分区：
文献类型：
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作者：
Joseph RW;Kapur P;Serie DJ;Parasramka M;Ho TH;Cheville JC;Frenkel E;Parker AS;Brugarolas J
在透明细胞肾细胞癌中，BAP1和PBRM1是2个最常见的突变基因（分别为10% - 15%和40% - 50%）。我们试图确定透明细胞肾细胞癌中PBRM1和BAP1表达的预后意义。我们使用免疫组织化学方法评估了1479例先前BAP1染色的原发性透明细胞肾细胞癌肿瘤中PBRM1蛋白的表达。集中病理学家对所有病例进行检查，并将肿瘤分为PBRM1和BAP1阳性或缺失。Kaplan-Meier和Cox回归模型用于评估PBRM1和BAP1表达与肾细胞癌死亡风险和转移风险的关系，调整年龄和梅奥诊所SSIGN（分期、大小、分级和坏死）评分后。PBRM1和BAP1在40.1%的肿瘤中表达为PBRM1+ BAP1+， PBRM1 - BAP1+ 48.6%, PBRM1+ BAP1 - 8.7%, PBRM1 - BAP1 - 1.8%。同一肿瘤中PBRM1和BAP1丢失的发生率显著低于预期（实际1.8% vs预期5.3%,p <0.0001）。与PBRM1+ BAP1+肿瘤患者相比，PBRM1 - BAP1+肿瘤患者更容易死于肾癌（HR 1.39, p = 0.035），其次是PBRM1+ BAP1 -和PBRM1 - BAP1 -肿瘤患者（HR分别为3.25和5.2,p <0.001）。PBRM1和BAP1的表达并未给SSIGN评分增加独立的预后信息。PBRM1和BAP1的表达确定了透明细胞肾细胞癌患者的4个临床亚组，这些亚组的临床结果不同。当针对PBRM1和BAP1下游通路的治疗方法开发出来后，这些生物标志物的临床价值将得到充分实现。
In clear cell renal cell carcinoma BAP1 and PBRM1 are 2 of the most commonly mutated genes (10% to 15% and 40% to 50%, respectively). We sought to determine the prognostic significance of PBRM1 and BAP1 expression in clear cell renal cell carcinoma. We used immunohistochemistry to assess PBRM1 protein expression in 1,479 primary clear cell renal cell carcinoma tumors that were previously stained for BAP1. A centralized pathologist reviewed all cases and categorized tumors as positive or deficient for PBRM1 and BAP1. Kaplan-Meier and Cox regression models were used to evaluate association of PBRM1 and BAP1 expression with the risk of death from renal cell carcinoma and the risk of metastasis after adjustment for age and the Mayo Clinic SSIGN (stage, size, grade and necrosis) score. PBRM1 and BAP1 expression was PBRM1+ BAP1+ in 40.1% of tumors, PBRM1− BAP1+ in 48.6%, PBRM1+ BAP1− in 8.7% and PBRM1− BAP1− in 1.8%. The incidence of PBRM1 and BAP1 loss in the same tumor was significantly lower than expected (actual 1.8% vs expected 5.3%, p <0.0001). Compared to patients with PBRM1+ BAP1+ tumors those with PBRM1− BAP1+ lesions were more likely to die of renal cell carcinoma (HR 1.39, p = 0.035), followed by those with PBRM1+ BAP1− and PBRM1− BAP1− tumors (HR 3.25 and 5.2, respectively, each p <0.001). PBRM1 and BAP1 expression did not add independent prognostic information to the SSIGN score. PBRM1 and BAP1 expression identified 4 clinical subgroups of patients with clear cell renal cell carcinoma who had divergent clinical outcomes. The clinical value of these biomarkers will be fully realized when therapies targeting pathways downstream of PBRM1 and BAP1 are developed.