BAP1 免疫组化预测多机构队列中透明细胞肾细胞癌患者的预后。
BAP1 immunohistochemistry predicts outcomes in a multi-institutional cohort with clear cell renal cell carcinoma.
机构信息
Department of Pathology (PK), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Urology (PK, YL, VM), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Internal Medicine (JB), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Developmental Biology (JB), University of Texas Southwestern Medical Center, Dallas, Texas; Simmons Cancer Center (XJX, JB), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Urology, Penn State Milton S. Hershey Medical Center (JDR), Hershey, Pennsylvania; Department of Pathology, University of Pittsburgh Medical Center (MTT), Pittsburgh, Pennsylvania; Department of Urology, University of Munich (PN, AB), Munich, Germany; Department of Urology, Paracelsus-Klinik Golzheim, Dusseldorf, Germany (PB); Department of Urology, Central Hospital of Bolzano (CS), Bolzano, Italy; Department of Urology, Medical University of Vienna, Vienna General Hospital (CS, SFS), Vienna, Austria; Department of Urology and Pathology, University of Rennes (KB, NR-L), Rennes, France.
Department of Pathology (PK), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Urology (PK, YL, VM), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Internal Medicine (JB), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Developmental Biology (JB), University of Texas Southwestern Medical Center, Dallas, Texas; Simmons Cancer Center (XJX, JB), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Urology, Penn State Milton S. Hershey Medical Center (JDR), Hershey, Pennsylvania; Department of Pathology, University of Pittsburgh Medical Center (MTT), Pittsburgh, Pennsylvania; Department of Urology, University of Munich (PN, AB), Munich, Germany; Department of Urology, Paracelsus-Klinik Golzheim, Dusseldorf, Germany (PB); Department of Urology, Central Hospital of Bolzano (CS), Bolzano, Italy; Department of Urology, Medical University of Vienna, Vienna General Hospital (CS, SFS), Vienna, Austria; Department of Urology and Pathology, University of Rennes (KB, NR-L), Rennes, France.
出版信息
J Urol. 2014 Mar;191(3):603-10. doi: 10.1016/j.juro.2013.09.041. Epub 2013 Sep 25.
PURPOSE
Mutations in the tumor suppressor gene BAP1 occur in approximately 15% of clear cell renal cell carcinoma cases. Sequencing efforts demonstrated worse outcomes in patients with BAP1 mutated clear cell renal cell carcinoma. We investigated the clinicopathological significance and oncologic outcomes of BAP1 loss using a previously validated immunohistochemical assay.
MATERIALS AND METHODS
Immunohistochemistry for BAP1 was performed on tissue microarray sections from 559 nonmetastatic clear cell renal cell carcinoma cases treated with nephrectomy at multiple institutions. The association of BAP1 expression with clinicopathological parameters was analyzed using the Wilcoxon rank sum and Cochran-Mantel-Haenszel tests. Survival was assessed by Cox regression analysis, which also identified independent predictors of time dependent outcomes.
RESULTS
At a median followup of 50 months (range 0 to 183) 86 of 483 patients (17.8%) experienced recurrence and 121 of 559 (21.6%) had died. BAP1 was negative in 82 of 559 tumors (14.7%). BAP1 loss was associated with adverse clinicopathological variables, including high Fuhrman grade (p <0.0001), advanced pT stage (p = 0.0021), sarcomatoid dedifferentiation (p = 0.0001) and necrosis (p <0.0001). Cox regression revealed that patients with BAP1 negative tumors had significantly worse disease-free survival (HR 2.9, 95% CI 1.8-4.7, p <0.0001) and overall survival (HR 2.0, 95% CI 1.3-3.1, p = 0.0010) than patients with BAP1 positive tumors.
CONCLUSIONS
Immunohistochemistry for BAP1 serves as a powerful marker to predict poor oncologic outcomes and adverse clinicopathological features in patients with nonmetastatic clear cell renal cell carcinoma. BAP1 assessment using immunohistochemistry on needle biopsy may benefit preoperative risk stratification and guide treatment planning in the future.
目的
肿瘤抑制基因 BAP1 的突变约发生在 15%的透明细胞肾细胞癌病例中。测序研究表明，BAP1 突变的透明细胞肾细胞癌患者的预后更差。我们使用先前验证的免疫组织化学检测方法研究了 BAP1 缺失的临床病理意义和肿瘤学结果。
材料与方法
对 559 例来自多个机构的接受肾切除术治疗的非转移性透明细胞肾细胞癌病例的组织微阵列切片进行 BAP1 免疫组织化学检测。使用 Wilcoxon 秩和检验和 Cochran-Mantel-Haenszel 检验分析 BAP1 表达与临床病理参数之间的关系。通过 Cox 回归分析评估生存情况，该分析还确定了与时间相关结果的独立预测因素。
结果
在中位随访 50 个月（范围 0 至 183）时，483 例患者中有 86 例（17.8%）复发，559 例患者中有 121 例（21.6%）死亡。在 559 例肿瘤中，有 82 例（14.7%）的 BAP1 呈阴性。BAP1 缺失与不良临床病理变量相关，包括高 Fuhrman 分级（p<0.0001）、高级 pT 分期（p=0.0021）、肉瘤样去分化（p=0.0001）和坏死（p<0.0001）。Cox 回归分析显示，BAP1 阴性肿瘤患者的无病生存率（HR 2.9，95%CI 1.8-4.7，p<0.0001）和总生存率（HR 2.0，95%CI 1.3-3.1，p=0.0010）明显低于 BAP1 阳性肿瘤患者。
结论
BAP1 的免疫组织化学检测可作为预测非转移性透明细胞肾细胞癌患者不良肿瘤学结果和不良临床病理特征的有力标志物。未来，在进行术前风险分层和指导治疗计划时，可通过对针吸活检标本进行 BAP1 评估来获益。
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