Differential diagnosis of solitary fibrous tumors: A study of 454 soft tissue tumors indicating the diagnostic value of nuclear STAT6 relocation and ALDH1 expression combined with in situ proximity ligation assay
Differential diagnosis of solitary fibrous tumors: A study of 454 soft tissue tumors indicating the diagnostic value of nuclear STAT6 relocation and ALDH1 expression combined with in situ proximity ligation assay
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DOI：
10.3892/ijo.2015.2975
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发表时间：
2015-06-01
影响因子：
5.2
通讯作者：
Wardelmann, Eva
中科院分区：
文献类型：
--
作者：
Ouladan, Shaida;Trautmann, Marcel;Wardelmann, Eva
孤立性纤维肿瘤是一种罕见的间叶性肿瘤，其形态和临床病理特征各异。支持性免疫组化标记物如CD 34、CD 99、BCL 2和LSD 1常用于SFT的鉴别诊断，尽管没有一种标记物具有足够的敏感性或特异性。本研究的目的是检查最具差异性的标志物，以可靠地区分SFTs和组织学模拟物。我们研究了STAT 6、NAB 2、ALDH 1、GRIA 2和IGF 2在454例综合性软组织肿瘤中的表达，包括来自80例SFT和374例其他间叶肿瘤的福尔马林固定石蜡包埋（FFPE）组织样本。采用Duo link原位邻位连接法（PLA）检测NAB 2-STAT 6融合蛋白。STAT 6在所有80例SFT中均表达，核染色强度为中-强。相比之下，只有4/374（1%）的非SFT间充质肿瘤显示核STAT 6染色模式。NAB 2和IGF 2在SFT和非SFT病例中均呈强表达。GRIA 2免疫反应阳性率分别为64%（SFT）和8%（非SFT）。76%（SFT）的ALDH 1表达为中强，而只有2个非SFT病变显示ALDH 1免疫反应阳性。此外，在71/78（91%）的SFT病例中通过PLA指示NAB 2-STAT 6融合蛋白的存在。核内STAT 6和胞浆内ALDH 1表达是鉴别诊断SFT最敏感和特异的标志物。Duolink原位邻位连接法可用于检测绝大多数SFT中NAB 2-STAT 6融合蛋白的表达。
Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms, displaying variable morphological and clinicopathological features. Supportive immunohistochemical markers such as CD34, CD99, BCL2 and LSD1 are commonly applied in the differential diagnosis of SFTs, although none is sufficiently sensitive or specific enough. The aim of the present study was to examine the most differential markers for the reliable distinction of SFTs from histological mimics. We investigated the expression of STAT6, NAB2, ALDH1, GRIA2 and IGF2 in 454 comprehensive soft tissue tumors, comprising formalin-fixed paraffin-embedded (FFPE) tissue samples from 80 SFTs and 374 other mesenchymal tumors. The Duo link in situ proximity ligation assay (PLA) was adopted for the detection of NAB2-STAT6 fusion proteins. STAT6 was expressed in all 80 SFT cases with a moderate-strong nuclear staining intensity. In contrast, only 4/374 (1%) non-SFT mesenchymal tumors showed a nuclear STAT6 staining pattern. Strong expression of NAB2 and IGF2 was detected in SFT and non-SFT cases. Positive GRIA2 immunoreactivity was found in 64% (SFT) and 8% (non-SFT), respectively. Expression of ALDH1 was moderate-strong in 76% (SFT), whereas only 2 non-SFT lesions showed positive ALDH1 immunoreactivity. Moreover, the presence of NAB2-STAT6 fusion proteins was indicated in 71/78 (91%) SFT cases by PLA. Nuclear STAT6 and cytoplasmic ALDH1 expression are the most sensitive and specific markers in the differential diagnosis of SFTs. Furthermore, application of Duolink in situ proximity ligation assay can be helpful to detect the NAB2-STAT6 fusion protein in the majority of SFTs.