According to the 2019 WHO classification of breast tumors, neuroendocrine neoplasms (NENs) are classified into well-differentiated NE tumors (NET) and poorly differentiated NE carcinomas (NEC), while other breast cancers (BCs) of special and no special type with neuroendocrine (NE) features are not incorporated in this scheme anymore. We aimed to assess whether INSM1, a novel NE marker, could have a role in breast NEN subtyping. We selected 63 BCs operated from 2003 to 2018, classified as BCs with NE features, with available clinico-pathological data. Following 2019 WHO criteria, this cohort was reclassified into 37 NETs/NECs, the remaining 26 tumors representing solid-papillary (7), mucinous (7), and mixed type (12) carcinomas with NE differentiation. Chromogranin A (CGA) and synaptophysin (SYN) immunostains were reviewed, and INSM1 was tested by immunohistochemistry. Thirty CGA- and SYN-negative no special type BCs served as negative control. INSM1 was expressed in 52/63 cases of the whole cohort (82.54%). INSM1 positive and negative cases had no significantly different clinico-pathological characteristics. INSM1 expression was not significantly different between the newly reclassified NET/NEC group and other BCs with NE features. No immunoexpression was observed in control BCs. The sensitivity and specificity of INSM1 for the NE phenotype was 82.5% and 100%, respectively, compared to 61.9% and 100% for CGA, and 95.2 and 100% for SYN. In conclusion, INSM1 is as accurate as traditional NE biomarkers to identify NE differentiation in BC. In analogy to standard NE markers, INSM1 could not distinguish NET and NEC from the other BC histotypes with NE differentiation.

根据 2019 年 WHO 乳腺肿瘤分类，神经内分泌肿瘤（NENs）分为高分化 NE 肿瘤（NET）和低分化 NE 癌（NEC）。 (NE) 功能不再包含在此方案中。我们旨在评估新的 NE 标记 INSM1 是否可能在乳腺 NEN 亚型中发挥作用。我们选择了 2003 年至 2018 年运营的 63 例 BC，归类为具有 NE 特征的 BC，具有可用的临床病理学数据。根据 2019 年 WHO 标准，该队列被重新分类为 37 个 NET/NEC，其余 26 个肿瘤代表实体乳头状 (7)、粘液性 (7) 和混合型 (12) 具有 NE 分化的癌。回顾了嗜铬粒蛋白 A (CGA) 和突触素 (SYN) 免疫染色，免疫组化检测INSM1。三十个 CGA 和 SYN 阴性无特殊类型的 BC 作为阴性对照。INSM1 在整个队列的 52/63 例（82.54%）中表达。INSM1阳性和阴性病例的临床病理特征无显着差异。INSM1 表达在新重新分类的 NET/NEC 组与其他具有 NE 特征的 BC 之间没有显着差异。在对照 BCs 中未观察到免疫表达。INSM1 对 NE 表型的敏感性和特异性分别为 82.5% 和 100%，而 CGA 为 61.9% 和 100%，SYN 为 95.2% 和 100%。总之，INSM1 与传统的 NE 生物标志物一样准确，可识别 BC 中的 NE 分化。与标准 NE 标记类似，INSM1 无法将 NET 和 NEC 与其他具有 NE 分化的 BC 组织型区分开来。