Molecular confirmation of t(6;11)(p21;q12) renal cell carcinoma in archival paraffin-embedded material using a break-apart TFEB FISH assay expands its clinicopathologic spectrum.
Molecular confirmation of t(6;11)(p21;q12) renal cell carcinoma in archival paraffin-embedded material using a break-apart TFEB FISH assay expands its clinicopathologic spectrum.
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DOI：
10.1097/pas.0b013e3182613d8f
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发表时间：
2012-10
期刊：
影响因子：
--
通讯作者：
Griffin CA
中科院分区：
文献类型：
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作者：
Argani P;Yonescu R;Morsberger L;Morris K;Netto GJ;Smith N;Gonzalez N;Illei PB;Ladanyi M;Griffin CA
肾细胞癌(RCC)的一个亚型是t(6；11)(p21；q12)，它导致未翻译的Alpha(MALAT1)基因与TFEB基因融合。仅报告了21例t(6；11)RCC遗传确诊病例。该肿瘤典型地表现为独特的双时相形态，包括较大的上皮样细胞和聚集在基底膜周围的较小的细胞；然而，其形态的全谱尚不清楚。T(6；11)RCC与大多数传统RCC的不同之处在于，它们持续表达黑素细胞免疫组织化学(IHC)标记，如HMB45和Melan A，以及半胱氨酸蛋白酶组织蛋白K，但通常不表达上皮标记，如细胞角蛋白。TFEB-IHC已被证实对档案材料中t(6；11)RCC的诊断有用，因为天然的TFEB是通过基因融合的启动子替换而上调的。然而，IHC高度依赖固定，已被证明对TFEB特别困难。在福尔马林固定的石蜡包埋的档案材料中，一种有效的荧光原位杂交(FISH)方法用于t(6；11)RCC的分子确认尚未见报道。在此，我们报告了一种诊断t(6；11)(p21；q12)肾细胞癌的分离TFEB FISH检测方法。我们对4例遗传确诊病例和76例相关预期阴性对照病例进行了验证，并用该方法报告了8例新病例，扩大了t(6；11)RCC的临床病理范围。另一例先前报告的TFEB IHC阳性病例由TFEB FISH在46年前的档案材料中确认。总之，TFEB FISH是一种可靠的、临床有效的检测方法，可以在档案材料中确认t(6；11)肾细胞癌的诊断，并且应该可以对这种最近被确认的肿瘤实体进行更全面的临床病理描述。
A subset of renal cell carcinomas (RCCs) is characterized by t(6;11)(p21;q12), which results in fusion of the untranslated Alpha (MALAT1) gene to the TFEB gene. Only 21 genetically confirmed cases of t(6;11) RCCs have been reported. This neoplasm typically demonstrates a distinctive biphasic morphology, comprising larger epithelioid cells and smaller cells clustered around basement membrane material; however, the full spectrum of its morphologic appearances is not known. The t(6;11) RCCs differ from most conventional RCCs in that they consistently express melanocytic immunohistochemical (IHC) markers such as HMB45 and Melan A and the cysteine protease cathepsin K but are often negative for epithelial markers such as cytokeratins. TFEB IHC has been proven to be useful to confirm the diagnosis of t(6;11) RCCs in archival material, because native TFEB is upregulated through promoter substitution by the gene fusion. However, IHC is highly fixation dependent and has been proven to be particularly difficult for TFEB. A validated fluorescence in situ hybridization (FISH) assay for molecular confirmation of the t(6;11) RCC in archival formalin-fixed, paraffin-embedded material has not been previously reported. We report herein the development of a break-apart TFEB FISH assay for the diagnosis of t(6;11)(p21;q12) RCCs. We validated the assay on 4 genetically confirmed cases and 76 relevant expected negative control cases and used the assay to report 8 new cases that expand the clinicopathologic spectrum of t(6;11) RCCs. An additional previously reported TFEB IHC-positive case was confirmed by TFEB FISH in 46-year-old archival material. In conclusion, TFEB FISH is a robust, clinically validated assay that can confirm the diagnosis of t(6;11) RCC in archival material and should allow a more comprehensive clinicopathologic delineation of this recently recognized neoplastic entity.