Surgical Pathology, SA Pathology at the Royal Adelaide Hospital, BreastScreen SA, Discipline of Medicine, Adelaide University.
Surgical Pathology, SA Pathology at the Royal Adelaide Hospital.
Appl Immunohistochem Mol Morphol. 2023 Feb 1;31(2):101-106. doi: 10.1097/PAI.0000000000001098. Epub 2023 Jan 25.
The discovery of almost invariable mouse double minute 2 (MDM2) amplification among atypical lipomatous tumors (ALT)/well-differentiated liposarcoma and dedifferentiated liposarcoma is incorporated into the contemporary diagnostic workup of fatty lesions. MDM2 amplifications are also found frequently in intimal sarcomas and in low-grade osteogenic sarcoma. At present, fluorescence in situ hybridization (FISH) is the reference test for MDM2 assessment. We are interested in evaluating silver in situ hybridization (SISH) for this purpose. Between October 2016 and May 2020, in 192 consecutive cases requiring MDM2 FISH, SISH was also performed concurrently, including 77 (40.1%) core biopsies and 115 (58.9%) surgical specimens. The mean patient age was 61.0 years. SISH results were available overnight or within 48 hours if repeat testing was required. FISH results were available within 2 to 5 weeks. The cost of SISH was one third of FISH. FISH demonstrated MDM2 amplification in 44 cases (23.6%), was negative in 144 cases (74.4%) and nondiagnostic in 4 decalcified cases (2.0%). SISH showed MDM2 amplification in 33 cases (17.2%), no amplification in 119 cases (62.0%), and indeterminate results because of poor signal in 40 (20.8%) cases. All 33 (100%) SISH-amplified tumors and 113 of 119 (95.0%) nonamplified results were confirmed by FISH. There were no clear differences in the performance of SISH on NCB versus surgical specimens. The overall performance indices of SISH are sensitivity 75%, specificity 78.5%, positive predictive value 100%, and negative predictive value 95.8%. FISH is not required when SISH is clearly amplified. This is clinically useful and improves efficiency. Nonamplified SISH results provide early indications of the likely FISH findings, but there is a 4.2% chance of FISH being positive. At present, the main drawback of SISH is the high rate of nondiagnostic tests. Optimization of SISH signal detection to reduce the proportion of indeterminate results is our current focus.
在非典型性脂肪肉瘤（ALT）/高分化脂肪肉瘤和去分化脂肪肉瘤中，几乎普遍存在鼠双微体 2（MDM2）扩增的发现已纳入脂肪病变的当代诊断。MDM2 扩增也经常发生在内膜肉瘤和低度骨肉瘤中。目前，荧光原位杂交（FISH）是 MDM2 评估的参考试验。我们有兴趣评估银原位杂交（SISH）是否可以用于此目的。在 2016 年 10 月至 2020 年 5 月期间，在需要进行 MDM2 FISH 的 192 例连续病例中，同时进行了 SISH 检测，包括 77 例（40.1%）核心活检和 115 例（58.9%）手术标本。患者的平均年龄为 61.0 岁。如果需要重复测试，则 SISH 结果可在一夜之间或 48 小时内获得。FISH 结果可在 2 至 5 周内获得。SISH 的成本为 FISH 的三分之一。FISH 在 44 例（23.6%）中显示 MDM2 扩增，在 144 例（74.4%）中为阴性，在 4 例脱钙病例（2.0%）中为非诊断性。SISH 显示 MDM2 扩增 33 例（17.2%），无扩增 119 例（62.0%），40 例（20.8%）信号不良结果不确定。所有 33 例（100%）SISH 扩增肿瘤和 119 例（95.0%）非扩增结果均通过 FISH 得到确认。SISH 在 NCB 与手术标本上的性能没有明显差异。SISH 的总体性能指标为灵敏度 75%，特异性 78.5%，阳性预测值 100%，阴性预测值 95.8%。当 SISH 明显扩增时，不需要进行 FISH。这在临床上很有用，可以提高效率。非扩增的 SISH 结果提供了可能的 FISH 发现的早期迹象，但 FISH 阳性的可能性为 4.2%。目前，SISH 的主要缺点是无法诊断的检测比例较高。优化 SISH 信号检测以减少不确定结果的比例是我们目前的重点。
