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T细胞相关蛋白在乳腺导管癌中的表达

Expression of T cell-related proteins in breast ductal carcinoma .

作者信息

Shin Eunah, Kim Hye Min, Koo Ja Seung

机构信息

Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.

出版信息

Histol Histopathol. 2025 Apr;40(4):467-475. doi: 10.14670/HH-18-805. Epub 2024 Sep 2.

Abstract

This study aims to explore the expression of T cell subtype markers within the immune cells constituting the tumor microenvironment of ductal carcinoma (DCIS) and to assess its implications. A tissue microarray comprising 191 cases of breast DCIS was created, and immunohistochemistry staining for T cell subtype markers (STAT3, STAT4, STAT-6, and FOXP3) was conducted. The DCIS cases were categorized into luminal, HER-2, and TNBC (Triple-negative breast cancer) types based on ER, PR, HER-2, and Ki-67 results. Additionally, they were classified as low-TIL (tumor-infiltrating lymphocytes) (<10%) or high-TIL (≥10%) types according to stromal TIL. Results revealed that 54.6% were luminal, 39.5% HER-2, and 5.9% TNBC. STAT3 exhibited a high positivity rate in luminal-type tumor cells, while STAT3, STAT4, STAT6, and FOXP3 showed elevated positivity rates in TNBC immune cells (<0.05). Furthermore, a higher positivity rate was observed in high-TIL immune cells compared with low-TIL (<0.001). The strongest agreement between T cell subtype markers in immune cells was found between STAT3 and STAT4 (OA=83.7%, κ=0.658), whereas the lowest was between STAT4 and FOXP3 (OA=71.7%, κ=0.370). In immune cells, STAT3 and STAT4 positivity correlated with necrosis (<0.001), and the absence of positivity in all immune cell-related proteins in DCIS with necrosis was associated with poor prognosis (=0.013). In conclusion, the immune cells in DCIS exhibit positivity for diverse T cell subtype markers, with TNBC and high-TIL DCIS displaying heightened positivity.

摘要

本研究旨在探讨构成导管原位癌(DCIS)肿瘤微环境的免疫细胞内T细胞亚型标志物的表达情况,并评估其意义。构建了包含191例乳腺DCIS病例的组织微阵列,并对T细胞亚型标志物(STAT3、STAT4、STAT-6和FOXP3)进行免疫组织化学染色。根据雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER-2)和Ki-67结果,将DCIS病例分为管腔型、HER-2型和三阴性乳腺癌(TNBC)型。此外,根据基质肿瘤浸润淋巴细胞(TIL)将其分为低TIL(<10%)或高TIL(≥10%)型。结果显示,管腔型占54.6%,HER-2型占39.5%,TNBC型占5.9%。STAT3在管腔型肿瘤细胞中显示出较高的阳性率,而STAT3、STAT4、STAT6和FOXP3在TNBC免疫细胞中显示出升高的阳性率(<0.05)。此外,高TIL免疫细胞中的阳性率高于低TIL(<0.001)。免疫细胞中T细胞亚型标志物之间最强的一致性出现在STAT3和STAT4之间(观察一致性=83.7%,κ=0.658),而最低的出现在STAT4和FOXP3之间(观察一致性=71.7%,κ=0.370)。在免疫细胞中,STAT3和STAT4阳性与坏死相关(<0.001),DCIS伴坏死中所有免疫细胞相关蛋白均无阳性与预后不良相关(=0.013)。总之,DCIS中的免疫细胞对多种T细胞亚型标志物呈阳性,TNBC和高TIL DCIS显示出更高的阳性率。

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