EWSR1-ATF1 Fusion Is a Novel and Consistent Finding in Hyalinizing Clear-Cell Carcinoma of Salivary Gland
EWSR1-ATF1 Fusion Is a Novel and Consistent Finding in Hyalinizing Clear-Cell Carcinoma of Salivary Gland
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DOI：
10.1002/gcc.20881
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发表时间：
2011-07-01
影响因子：
3.7
通讯作者：
Weinreb, Ilan
中科院分区：
文献类型：
--
作者：
Antonescu, Cristina R.;Katabi, Nora;Weinreb, Ilan
透明化透明细胞癌是一种罕见的低度恶性涎腺肿瘤，具有独特的透明细胞形态、透明化模式以及局灶性粘液分化。然而，与其他唾液腺肿瘤，如上皮-肌上皮癌（EMCa），唾液肌上皮癌和粘液表皮样癌（MEC）存在组织学重叠。HCCC与其形态学模拟物之间的潜在关系尚未在遗传水平上进行研究。在这项研究中，我们进行了一个分子分析的MAML 2，常见于MEC，和EWSR 1，参与“软组织肌上皮肿瘤”（SMET）通过与POU 5 F1，PBX 1，或ZNF 444融合的重排的存在。应用荧光原位杂交技术检测23例HCCC中MAML 2、EWSR 1、FUS、POU 5 F1、PBX 1和ZNF 444的异常。所有病例（14例中0例）的MAML 2 FISH均为阴性，包括粘液分化的病例（7例中0例）。在22例HCC中有18例（82%）发现EWSR 1重排，而在FUS、POU 5 F1、PBX 1或ZNF 444中未发现断裂信号。RT-PCR证实EWSR 1-ATF 1融合蛋白在HCCC中的3 'RACE扩增产物中存在。14例EWSR 1重排的HCCC中有13例（93%）进一步通过FISH分析证实了ATF 1参与。相比之下，所有测试的对照病例，其中包括5例EMCa和3例MEC（具有透明细胞），均为EWSR 1和ATF 1重排阴性。大多数HCC中EWSR 1-ATF 1融合的存在可靠地将这些肿瘤与其组织学模拟物分开。与MEC的区别尤其重要，因为传统的MEC分级方案高估了这些惰性HCCC的分级，可能会影响治疗。(C)2011 Wiley-Liss，Inc.
Hyalinizing clear-cell carcinoma (HCCC) is a rare, low-grade salivary gland tumor with distinctive clear-cell morphology and pattern of hyalinization as well as focal mucinous differentiation. However, histological overlap exists with other salivary gland tumors, such as epithelial-myoepithelial carcinoma (EMCa), salivary myoepithelial carcinoma, and mucoepidermoid carcinoma (MEC). The potential relationship between HCCC and its morphological mimics has not been yet investigated at the genetic level. In this study, we conducted a molecular analysis for the presence of rearrangements in MAML2, commonly seen in MECs, and EWSR1, involved in "soft tissue myoepithelial tumors" (SMET) by fusion with POU5F1, PBX1, or ZNF444. Fluorescence in situ hybridization (FISH) was performed on 23 HCCC cases for abnormalities in MAML2, EWSR1, FUS, POU5F1, PBX1, and ZNF444. FISH for MAML2 was negative in all cases (0 of 14), including those with mucinous differentiation (0 of 7). An EWSR1 rearrangement was identified in 18 of 22 HCCCs (82%), while no break-apart signals were seen in FUS, POU5F1, PBX1, or ZNF444. 3'RACE on an EWSR1 rearranged HCCC identified an EWSR1-ATF1 fusion, which was confirmed by RT-PCR. ATF1 involvement was further confirmed by FISH analysis in 13 of 14 EWSR1-rearranged HCCC cases (93%). In contrast, all control cases tested, including among others 5 EMCa and 3 MEC with clear cells, were negative for EWSR1 and ATF1 rearrangements. The presence of EWSR1-ATF1 fusion in most HCCCs reliably separates these tumors from its histological mimics. The distinction from MEC is particularly important, as conventional MEC grading schemes overgrade these indolent HCCCs, potentially impacting on treatment. (C) 2011 Wiley-Liss, Inc.