Shin Eunah, Kim Hye Min, Koo Ja Seung
Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.
Histol Histopathol. 2025 Apr;40(4):467-475. doi: 10.14670/HH-18-805. Epub 2024 Sep 2.
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.
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。
