Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Mod Pathol. 2022 Nov;35(11):1587-1595. doi: 10.1038/s41379-022-01117-4. Epub 2022 Jun 14.
:AFF2 carcinoma of the sinonasal tract is an emerging entity. The tumor is typically characterized by papillary proliferation of non-keratinizing squamous epithelial cells with monotonous cytologic features, which may mimic other sinonasal tumors. The confirmation of this gene fusion has thus far relied solely on next-generation sequencing, fluorescence in situ hybridization (FISH), or reverse transcription polymerase chain reaction (RT-PCR). This current study aimed to validate an immunohistochemical assay for AFF2 C-terminus as an ancillary marker. We first analyzed publicly available RNA sequencing data of sinonasal tumors from the national center for biotechnology information (NCBI) sequence read archive and identified 3 DEK::AFF2 carcinomas out of 28 sinonasal tumors. The gene expression of AFF2 was significantly higher in the fusion-positive cases compared to the wild-type tumors (p < 0.001), while DEK was not. We then optimized an immunohistochemical assay with an anti-AFF2 C-terminus antibody for ancillary diagnosis. Seventeen DEK::AFF2 carcinomas, including 11 cases with predominantly low-grade morphology and one showing glandular differentiation, as well as 78 DEK FISH-negative sinonasal tumors were evaluated by AFF2 immunohistochemistry (IHC). Sixteen of the 17 DEK::AFF2 carcinomas showed nuclear AFF2 expression in ≥30% of tumor cells, including one decalcified case that failed FISH and RT-PCR confirmation. The one case that was negative for AFF2 IHC in the tumor cells also lacked expression in the internal positive control. It was thus considered a failure of the IHC rather than a truly negative case and was excluded from the statistical analysis. All DEK FISH-negative sinonasal tumors were negative for nuclear AFF2 expression. The nuclear expression of AFF2 IHC showed 100% sensitivity and specificity for DEK::AFF2 carcinoma. Accordingly, AFF2 IHC is a highly sensitive and specific ancillary marker that distinguishes DEK-AFF2 carcinoma from the other sinonasal tumors with overlapping morphological features and may be an especially useful alternative for decalcified specimens.
:AFF2 鼻旁窦肿瘤是一种新兴实体瘤。该肿瘤通常表现为非角化鳞状上皮细胞的乳头状增生，具有单调的细胞学特征，可能模仿其他鼻旁窦肿瘤。到目前为止，这种基因融合的确认仅依赖于下一代测序、荧光原位杂交（FISH）或逆转录聚合酶链反应（RT-PCR）。本研究旨在验证 AFF2 C 末端的免疫组织化学检测作为辅助标志物。我们首先分析了来自美国国立生物技术信息中心（NCBI）序列读取档案的公开可用的鼻旁窦肿瘤 RNA 测序数据，并在 28 例鼻旁窦肿瘤中发现了 3 例 DEK::AFF2 癌。与野生型肿瘤相比，融合阳性病例中 AFF2 的基因表达明显更高（p<0.001），而 DEK 则不然。然后，我们用抗 AFF2 C 末端抗体优化了免疫组织化学检测，用于辅助诊断。17 例 DEK::AFF2 癌，包括 11 例主要为低级别形态的病例和 1 例具有腺分化的病例，以及 78 例 DEK FISH 阴性的鼻旁窦肿瘤，通过 AFF2 免疫组织化学（IHC）进行评估。在 17 例 DEK::AFF2 癌中，有 16 例肿瘤细胞中核 AFF2 表达≥30%，包括 1 例脱钙病例，该病例的 FISH 和 RT-PCR 确认失败。肿瘤细胞中 AFF2 IHC 阴性的 1 例病例也缺乏内部阳性对照的表达。因此，它被认为是 IHC 失败而不是真正的阴性病例，并被排除在统计分析之外。所有 DEK FISH 阴性的鼻旁窦肿瘤均无核 AFF2 表达。AFF2 IHC 的核表达对 DEK::AFF2 癌具有 100%的敏感性和特异性。因此，AFF2 IHC 是一种高度敏感和特异的辅助标志物，可将 DEK-AFF2 癌与具有重叠形态特征的其他鼻旁窦肿瘤区分开来，并且可能是脱钙标本的特别有用的替代方法。
