Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Virchows Arch. 2020 Feb;476(2):295-305. doi: 10.1007/s00428-019-02640-7. Epub 2019 Aug 19.
Secretory carcinoma of the salivary gland is a newly recognized entity that morphologically resembles breast secretory carcinoma and has a characteristic t(12;15)(p13;q25) ETV6-NTRK3 translocation. Fluorescence in situ hybridization (FISH) or reverse transcription polymerase chain reaction (RT-PCR) analyses can detect the ETV6-NTRK3 fusion; however, both tests are expensive and not widely available. In this study, we aimed to determine whether pan-Trk immunohistochemistry (IHC) could detect ETV6-NTRK3 fusions as reliably as RT-PCR and FISH. We performed pan-Trk IHC in 70 salivary gland cancer samples, including secretory carcinomas, acinic cell carcinomas, and hybrid carcinomas. Nineteen tumors exhibited positive pan-Trk staining, including 16 secretory carcinomas, 2 hybrid carcinomas with a secretory carcinoma component, and 1 acinic cell carcinoma. Pan-Trk IHC staining was localized in the nucleus in 16 (84.2%) cases and in the cytoplasm and/or membrane in 3 (15.8%) cases. RT-PCR analysis for the ETV6-NTRK3 transcript was conducted in 45 samples; the fusion transcript was present in 11 of 12 secretory carcinomas and absent in 32 acinic cell carcinomas and 1 mucoepidermoid carcinoma. Pan-Trk IHC was positive in 10 of 11 salivary tumors that were positive for ETV6-NTRK3 by RT-PCR and negative in all 34 tumors that were negative for the fusion by RT-PCR. Therefore, in comparison with RT-PCR, pan-Trk IHC had a sensitivity of 90.9% and specificity of 100%. In conclusion, our data showed that pan-Trk IHC is a reasonable screening test for diagnosing secretory carcinoma of the salivary gland.
唾液腺癌是一种新认识的实体，在形态上类似于乳腺分泌癌，具有特征性的 t(12;15)(p13;q25)ETV6-NTRK3 易位。荧光原位杂交（FISH）或逆转录聚合酶链反应（RT-PCR）分析可以检测到 ETV6-NTRK3 融合；然而，这两种检测都很昂贵，并且不能广泛应用。在这项研究中，我们旨在确定泛-Trk 免疫组织化学（IHC）是否能像 RT-PCR 和 FISH 一样可靠地检测 ETV6-NTRK3 融合。我们对 70 例唾液腺癌样本（包括分泌癌、腺泡细胞癌和混合癌）进行了泛-Trk IHC 检测。19 例肿瘤表现出阳性的泛-Trk 染色，包括 16 例分泌癌、2 例具有分泌癌成分的混合癌和 1 例腺泡细胞癌。16 例（84.2%）病例的泛-Trk IHC 染色定位于细胞核，3 例（15.8%）病例定位于细胞质和/或细胞膜。对 45 例样本进行了 ETV6-NTRK3 转录的 RT-PCR 分析；融合转录本存在于 12 例分泌癌中的 11 例，不存在于 32 例腺泡细胞癌和 1 例黏液表皮样癌中。在 11 例通过 RT-PCR 检测到 ETV6-NTRK3 阳性的唾液腺肿瘤中，泛-Trk IHC 呈阳性，而在所有 34 例 RT-PCR 检测到融合阴性的肿瘤中，泛-Trk IHC 呈阴性。因此，与 RT-PCR 相比，泛-Trk IHC 的敏感性为 90.9%，特异性为 100%。总之，我们的数据表明，泛-Trk IHC 是诊断唾液腺癌的一种合理的筛选试验。
