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多溴-1(PBRM1)是 SWI/SNF 复合物亚基,是透明细胞肾细胞癌的预后标志物。

Polybromo-1 (PBRM1), a SWI/SNF complex subunit is a prognostic marker in clear cell renal cell carcinoma.

机构信息

Urology Division, A.C. Camargo Cancer Center, Sao Paulo, Brazil.

出版信息

BJU Int. 2014 May;113(5b):E157-63. doi: 10.1111/bju.12426. Epub 2013 Dec 2.

Abstract

OBJECTIVE

To analyse the immunohistochemical and mRNA expression of SWI/SNF (SWItch/Sucrose NonFermentable) complex subunit polybromo-1 (PBRM1) in clear cell renal cell carcinoma (ccRCC) and its impact on clinical outcomes.

PATIENTS AND METHODS

In all, 213 consecutive patients treated surgically for renal cell carcinoma (RCC) between 1992 and 2009 were selected. A single pathologist reviewed all cases to effect a uniform reclassification and determined the most representative tumour areas for construction of a tissue microarray. In addition, mRNA expression of PBRM1 was analysed by reverse transcriptase-polymerase chain reaction.

RESULTS

Of the 112-immunostained ccRCC specimens, 34 (30.4%) were PBRM1-negative, and 78 (69.6%) were PBRM1-positive. The protein expression of PBRM1 was associated with tumour stage (P < 0.001), clinical stage (P < 0.001), pN stage (P = 0.035) and tumour size (P = 0.002). PBRM1 mRNA expression was associated with clinical stage (P = 0.023), perinephric fat invasion (P = 0.008) and lymphovascular invasion (P = 0.042). PBRM1 significantly influenced tumour recurrence and tumour-related death. Disease-specific survival rates for patients whose specimens showed positive- and negative-PBRM1 expression were 89.7% and 70.6%, respectively (P = 0.017). Recurrence-free survival rates in patients with positive- and negative-expression of PBRM1 were 87.3% and 66.7%, respectively (P = 0.048).

CONCLUSIONS

PBRM1-negative expression is a markedly poor prognosis event in ccRCC. We encourage PBRM1 study by other groups in order to validate our findings and confirm its possible role as a useful marker in the management of patients with ccRCC.

摘要

目的

分析 SWI/SNF(Switch/Sucrose NonFermentable)复合物亚基多溴-1(PBRM1)在透明细胞肾细胞癌(ccRCC)中的免疫组织化学和 mRNA 表达及其对临床结局的影响。

患者和方法

共选择了 1992 年至 2009 年间接受手术治疗的 213 例连续肾细胞癌(RCC)患者。一名病理学家对所有病例进行了回顾性分析,以实现统一的重新分类,并确定构建组织微阵列的最具代表性的肿瘤区域。此外,还通过逆转录-聚合酶链反应分析了 PBRM1 的 mRNA 表达。

结果

在 112 例免疫组化染色的 ccRCC 标本中,34 例(30.4%)为 PBRM1 阴性,78 例(69.6%)为 PBRM1 阳性。PBRM1 蛋白表达与肿瘤分期(P < 0.001)、临床分期(P < 0.001)、pN 分期(P = 0.035)和肿瘤大小(P = 0.002)有关。PBRM1 mRNA 表达与临床分期(P = 0.023)、肾周脂肪浸润(P = 0.008)和血管淋巴管浸润(P = 0.042)有关。PBRM1 显著影响肿瘤复发和肿瘤相关死亡。PBRM1 表达阳性和阴性的患者肿瘤特异性生存率分别为 89.7%和 70.6%(P = 0.017)。PBRM1 表达阳性和阴性的患者无复发生存率分别为 87.3%和 66.7%(P = 0.048)。

结论

PBRM1 阴性表达是 ccRCC 中一个显著的预后不良事件。我们鼓励其他研究组对 PBRM1 进行研究,以验证我们的发现,并确认其作为透明细胞肾细胞癌患者管理中有用标志物的可能作用。

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