Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Clinical Education Center, Kyushu University Hospital, Fukuoka, Japan.
Pathol Int. 2021 Jan;71(1):51-59. doi: 10.1111/pin.13043. Epub 2020 Nov 6.
Solid papillary carcinoma (SPC) is a histological subtype of breast carcinomas. At least 50% of SPC show neuroendocrine differentiation. Insulinoma-associated protein 1 (INSM1) is a transcription factor now employed as a useful neuroendocrine marker. It is suppressed by the Notch signaling pathway in other neuroendocrine tumors. However, the usefulness of INSM1 as a neuroendocrine marker and the relationships between INSM1 and NOTCH receptors in SPC of the breast currently remain unclear. To clarify the usefulness of INSM1 as a neuroendocrine marker and the relationships between INSM1 and NOTCH receptors in SPC, we performed immunohistochemistry using 19 tissue specimens of SPC of the breast. We complementarily analyzed public RNA sequencing data on breast carcinomas. Immunohistochemical examinations revealed that the staining intensity of INSM1 was significantly higher in the neuroendocrine group than in the non-neuroendocrine group. Positive correlations were observed between INSM1 and synaptophysin (SYP), or chromogranin-A (CHGA). In all cases, NOTCH 2 and 3 were positive, while NOTCH 1 and 4 were negative. According to public RNA data analyses, there were positive correlations between INSM1 and SYP, or CHGA, and negative correlations between INSM1 and NOTCH1-3. INSM1 is useful as a diagnostic marker for SPC with neuroendocrine differentiation in the breast.
实性乳头状癌（SPC）是乳腺癌的一种组织学亚型。至少有 50%的 SPC 显示神经内分泌分化。胰岛素瘤相关蛋白 1（INSM1）是一种转录因子，现在被用作有用的神经内分泌标志物。在其他神经内分泌肿瘤中，它被 Notch 信号通路抑制。然而，INSM1 作为神经内分泌标志物的用途以及 INSM1 和 NOTCH 受体在乳腺 SPC 中的关系目前仍不清楚。为了阐明 INSM1 作为神经内分泌标志物的用途以及 INSM1 和 NOTCH 受体在乳腺 SPC 中的关系，我们使用 19 个乳腺 SPC 组织标本进行了免疫组织化学检查。我们还对乳腺癌的公共 RNA 测序数据进行了补充分析。免疫组织化学检查显示，INSM1 在神经内分泌组中的染色强度明显高于非神经内分泌组。INSM1 与突触素（SYP）或嗜铬粒蛋白 A（CHGA）之间存在正相关。在所有病例中，NOTCH2 和 3 均为阳性，而 NOTCH1 和 4 均为阴性。根据公共 RNA 数据分析，INSM1 与 SYP 或 CHGA 之间存在正相关，与 NOTCH1-3 之间存在负相关。INSM1 是乳腺具有神经内分泌分化的 SPC 的有用诊断标志物。
