- Stanford 团队在 1210 例骨与软组织肿瘤（全切片 + 组织芯片）中评估 USP6 RNA CISH；阳性定义为 >1% 病变细胞着色。
- 结节性筋膜炎阳性 92%（36/39），原发性动脉瘤样骨囊肿 85%（17/20）；分子确认 USP6 融合的病例全部阳性（15/15、8/8）。腱鞘富于细胞性纤维瘤与骨化性肌炎亦 3/3 阳性。
- 1145 例阴性对照（53 种其他肿瘤）中特异性高，但血管肉瘤、MPNST、癌肉瘤各有 1 例阳性——判读须结合形态，警惕孤立假阳性。
收录范围：PubMed 英文摘要及中文翻译（abstract-only）。原文为订阅制（Ovid/LWW 页面无开放全文），未采集全文、图表。
摘要
复发性 USP6 基因重排是部分间叶性肿瘤（包括结节性筋膜炎和动脉瘤样骨囊肿）的基础。这类重排使 USP6 受另一基因组成性激活启动子的调控，导致 USP6 过表达。近期在少量病例中已证实，以 RNA 显色原位杂交（CISH）检测 USP6 过表达可作为 USP6 重排肿瘤的替代标志物。为进一步评估 USP6 RNA CISH 的诊断价值，我们结合全组织切片与组织芯片，将其应用于 1210 例骨与软组织肿瘤。USP6 过表达定义为 >1% 的病变细胞出现 RNA CISH 着色，见于 92%（36/39）的结节性筋膜炎和 85%（17/20）的原发性动脉瘤样骨囊肿。经分子遗传学检测证实存在 USP6 融合的结节性筋膜炎（15/15）和原发性动脉瘤样骨囊肿（8/8）全部呈过表达阳性。其他 USP6 阳性的肿瘤包括腱鞘富于细胞性纤维瘤（3/3，100%）和骨化性肌炎（3/3，100%）。在代表 53 种其他肿瘤类型的 1145 例阴性对照中，USP6 RNA CISH 对 USP6 重排病变显示高度特异性，但在个别血管肉瘤（1/16，6%）、恶性外周神经鞘瘤（1/80，1%）和癌肉瘤（1/7，14%）中罕见阳性。综上，这些结果表明 USP6 RNA CISH 是一种有用的诊断工具；鉴于个别非 USP6 重排肿瘤罕见阳性，审慎判读仍是其成功应用的关键。
- A Stanford group evaluated USP6 RNA CISH in 1210 bone and soft tissue tumors (whole sections + TMAs); positivity was defined as staining in >1% of lesional cells.
- Positive in 92% (36/39) of nodular fasciitis and 85% (17/20) of primary ABC; all molecularly confirmed USP6-fused cases were positive (15/15, 8/8). Cellular fibroma of tendon sheath and myositis ossificans were also 3/3 positive.
- Highly specific across 1145 negative controls (53 tumor types), but single angiosarcoma, MPNST and carcinosarcoma cases stained — careful interpretation is required.
Scope: PubMed abstract only. The article is subscription-only (no open full text on the Ovid/LWW page), so full text, figures and tables were not collected.
Abstract
Recurrent USP6 gene rearrangements underlie a subset of mesenchymal neoplasms, including nodular fasciitis and aneurysmal bone cyst. These rearrangements place USP6 under the regulatory control of another gene's constitutively active promoter, resulting in USP6 overexpression. Recently, it has been demonstrated in a limited number of cases that detection of USP6 overexpression by RNA chromogenic in situ hybridization (CISH) can serve as a surrogate marker for USP6-rearranged tumors. To further assess the diagnostic utility of USP6 RNA CISH, we evaluated its application in 1210 bone and soft tissue tumors, using a combination of whole tissue sections and tissue microarrays. USP6 overexpression, defined as RNA CISH staining in >1% of lesional cells, was observed in 92% (36/39) of nodular fasciitis cases and in 85% (17/20) of primary aneurysmal bone cysts. All examples of nodular fasciitis (15/15) and primary aneurysmal bone cyst (8/8) with USP6 fusion confirmed by molecular genetic testing were positive for overexpression. Other tumors staining positive for USP6 included cellular fibroma of tendon sheath (3/3, 100%) and myositis ossificans (3/3, 100%). Although USP6 RNA CISH proved to be highly specific for USP6-rearranged lesions when assessed in 1145 negative control cases reflecting 53 other tumor types, positivity was rarely seen in isolated cases of angiosarcoma (1/16, 6%), malignant peripheral nerve sheath tumor (1/80, 1%), and carcinosarcoma (1/7, 14%). Taken together, these findings indicate that USP6 RNA CISH represents a useful diagnostic tool; careful interpretation remains critical to its successful implementation, given that isolated examples of non-USP6-rearranged tumors rarely stain positive.