Department of Pathology, Memorial Sloan Kettering Cancer Center, New York City, New York, 10065 USA.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York City, New York, 10065 USA.
Hum Pathol. 2022 Sep;127:102-111. doi: 10.1016/j.humpath.2022.06.003. Epub 2022 Jun 8.
INSM1, ASCL1, and POU2F3 are novel transcription factors involved in neuroendocrine (NE) differentiation of neoplasms in several organs, but data on their expression in breast carcinomas (BCs) are limited. We retrospectively evaluated the expression of these markers in a series of 97 BCs (58 with NE morphology and 39 with otherwise uncommon morphology) tested prospectively using immunohistochemistry (IHC). Nuclear staining in >50% of the cells was used as the positive cut-off. Thirty-two of the 97 BCs (33%) were INSM1-positive. INSM1-positivity correlated significantly with histologic type and presence of stromal mucin. INSM1 also correlated with synaptophysin and chromogranin, established markers of NE differentiation (P < .0001 and P = .0023, respectively). In BC with NE morphology, the expression of INSM1 supported NE differentiation, and INSM1 was more specific than synaptophysin and more sensitive and specific than chromogranin. INSM1 was the most expressed NE marker in 17 BCs. INSM1-positive BCs included 56% of solid papillary BCs, 88% of BCs with solid papillary features, and 75% of high-grade NE carcinomas. Of 35 BCs tested for POU2F3 and ASCL1, only 1 and 4 cases were positive, respectively. Our results show that INSM1 is a sensitive marker of NE differentiation in BC and should be included with synaptophysin and chromogranin in the IHC panel used to evaluate NE differentiation in BC with NE morphology. ASCL1 and POU2F3 are uncommon in BC and their routine assessment is not warranted.
INSM1、ASCL1 和 POU2F3 是几种器官的神经内分泌（NE）分化肿瘤中涉及的新型转录因子，但它们在乳腺癌（BC）中的表达数据有限。我们使用免疫组织化学（IHC）前瞻性评估了这些标志物在 97 例 BC （58 例具有 NE 形态，39 例具有其他罕见形态）中的表达。将细胞中核染色大于 50%的作为阳性截断值。97 例 BC 中有 32 例（33%）为 INSM1 阳性。INSM1 阳性与组织学类型和间质粘蛋白的存在显著相关。INSM1 还与突触素和嗜铬粒蛋白相关，这是 NE 分化的既定标志物（分别为 P<0.0001 和 P=0.0023）。在具有 NE 形态的 BC 中，INSM1 的表达支持 NE 分化，INSM1 比突触素更特异，比嗜铬粒蛋白更敏感和特异。INSM1 是 17 例 BC 中表达最高的 NE 标志物。INSM1 阳性的 BC 包括 56%的实性乳头状 BC、88%的具有实性乳头状特征的 BC 和 75%的高级别 NE 癌。在 35 例接受 POU2F3 和 ASCL1 检测的 BC 中，分别只有 1 例和 4 例阳性。我们的结果表明，INSM1 是 BC 中 NE 分化的敏感标志物，应与突触素和嗜铬粒蛋白一起包含在用于评估具有 NE 形态的 BC 中 NE 分化的 IHC 面板中。ASCL1 和 POU2F3 在 BC 中不常见，不需要常规评估。
