CRTC1-MAML2 and CRTC3-MAML2 Fusions Were Not Detected in Metaplastic Warthin Tumor and Metaplastic Pleomorphic Adenoma of Salivary Glands
CRTC1-MAML2 and CRTC3-MAML2 Fusions Were Not Detected in Metaplastic Warthin Tumor and Metaplastic Pleomorphic Adenoma of Salivary Glands
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DOI：
10.1097/pas.0000000000000065
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发表时间：
2013-11-01
影响因子：
5.6
通讯作者：
Michal, Michal
中科院分区：
文献类型：
--
作者：
Skalova, Alena;Vanecek, Tomas;Michal, Michal
复发性易位t（11;19）和t（11;15）分别导致CRTC 1-MAML 2或CRTC 3-MAML 2融合癌基因，在大比例的唾液腺粘液表皮样癌（MEC）中被鉴定，并对预后有影响。然而，关于这种易位的特异性，特别是关于其在腮腺沃辛瘤（WT）中的假定发生率，存在相互矛盾的数据，如在以前的一些病例中报道的。据推测，广泛的鳞状上皮化生可以解释在WT的一个子集中存在t（11;19）易位。我们评估了76例涎腺肿瘤，包括16例化生WT和8例多形性腺瘤（PA）伴鳞状和/或粘液化生，形态学上足以模仿MEC。分别采用巢式逆转录-聚合酶链反应和荧光原位杂交（FISH）检测CRTC 1-MAML 2和CRTC 3-MAML 2融合转录本和MAML 2基因断裂。16例化生WT均未检测到CRTC 1-MAML 2或CRTC 3-MAML 2融合基因，且FISH均未检测到MAML 2基因重排。同样，我们在任何伴有广泛鳞状/粘液化生的PA病例中均未检测到这些转录本或MAML 2基因断裂。为了比较，还对40例低度MEC进行了评价。CRTC 1-MAML 2融合基因阳性17例，CRTC 3-MAML 2融合基因阳性5例。分离探针FISH法检测25例低度恶性MEC中MAML 2基因重排。与低级别MEC相反，化生WT和化生PA均不携带易位t（11;19）和预期的t（11;15），分别导致CRTC 1-MAML 2和CRTC 3-MAML 2融合转录物和/或MAML 2基因重排。
The recurrent translocations t(11;19) and t(11;15) resulting in CRTC1-MAML2 or CRTC3-MAML2 fusion oncogenes, respectively, are identified in a large proportion of mucoepidermoid carcinomas (MECs) of the salivary gland and have impact on prognosis. However, there are conflicting data on the specificity of this translocation, in particular, on its putative occurrence in Warthin tumor (WT) of the parotid gland as reported in few previous cases. It was speculated that extensive squamous metaplasia could explain the presence of t(11;19) translocation in a subset of WTs. We evaluated 76 salivary gland tumors, including 16 cases of metaplastic WT and 8 cases of pleomorphic adenoma (PA) with squamous and/or mucinous metaplasia, extensive enough morphologically to mimic MEC. Detection of CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts and MAML2 gene break was performed using nested reverse transcription-polymerase chain reaction and fluorescence in situ hybridization (FISH), respectively. None of 16 analyzed metaplastic WTs showed positivity for fusion transcripts CRTC1-MAML2 or CRTC3-MAML2, and none showed rearrangement of the MAML2 gene by FISH. Similarly, we did not detect these transcripts or break of MAML2 gene in any case of PA with extensive squamous/mucinous metaplasia. For comparison, 40 cases of low-grade MEC were also evaluated. CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts were detected in 17 and 5 cases, respectively. The FISH method using break-apart probe demonstrated the MAML2 gene rearrangement in 25 cases of low-grade MEC. In contrast to low-grade MEC, neither metaplastic WTs nor metaplastic PAs harbored translocations t(11;19) and anticipated t(11;15) resulting in CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts, respectively, and/or MAML2 gene rearrangement.