Immune parameters associated with survival in metaplastic breast cancer
Immune parameters associated with survival in metaplastic breast cancer
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DOI：
10.1186/s13058-020-01330-6
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发表时间：
2020-08-18
影响因子：
7.4
通讯作者：
Yun, Jingping
中科院分区：
文献类型：
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作者：
Chao, Xue;Liu, Lili;Yun, Jingping
背景 化生性乳腺癌（MBC）是一种罕见的乳腺癌组织学类型，通常对标准治疗表现出耐药性，并且与不良预后相关。由于MBC的发病率低且成分复杂，其免疫微环境及其意义尚未明确。我们的目的是研究 MBC 中免疫参数的多样性，包括 TIL 子集和 PDL1/PD1 表达，及其与预后的相关性。方法纳入2006年1月至2017年12月诊断为MBC的60例患者。通过苏木精和伊红染色 (HE) 评估 TIL 的百分比 (%) 和定量（每 mm(2)）以及三级淋巴结构 (TLS) 的存在。通过免疫组织化学评估CD4+、CD8+ TIL（每mm(2)）和PD-1/PDL1表达的定量，并分析与临床病理学特征的关系。 PD1和PDL1的膜或细胞质表达≥1%被认为是阳性表达。结果 我们发现鳞状细胞癌 MBC（33/60，55%）表现出所有 MBC 亚型中大多数 TIL（p = 0.043）。 60 名患者中有 33 名 (50%) 患有非特殊类型的共存浸润性导管癌 (IDC-NST)，且 MBC 成分中 TIL 的平均百分比低于 NST 成分 (p < 0.001)。 30 名 (50%) 患者的肿瘤细胞中 PDL1 表达呈阳性 (>= 1%)，而 36 名 (60%) 患者的 TIL 中 PDL1 表达呈阳性 (>= 1%)。所有患者中有 27 名 (45%) 的肿瘤细胞 PD1 表达呈阳性 (>= 1%)，33 名 (55%) 的基质 TIL 呈 PD1 阳性 (>= 1%)。更多 CD8+ TIL 与肿瘤细胞的 PDL1 阳性表达以及基质细胞的 PD1 阳性表达相关。 MBC 中较多的基质 TILS (> 300/mm(2), 20%)、CD4+ TIL (> 250/mm(2)) 和 CD8+ TIL (> 70/mm(2)) 与较长的无病生存期相关。肿瘤细胞中 PDL1 (>= 1%) 和基质细胞中 PD1 (>= 1%) 的阳性表达也与较长的生存期相关。结论 MBC不同亚型及成分的免疫特征存在差异。免疫参数是 MBC 的关键预测因素，并为 MBC 患者应用免疫检查点疗法提供临床意义。
Background Metaplastic breast carcinoma (MBC) is a rare histological type of breast cancer, which commonly shows resistance to standard therapies and is associated with poor prognosis. The immune microenvironment in MBC and its significance has not been well established due to its low incurrence rate and complex components. We aimed to investigate the diversity of immune parameters including subsets of TILs and PDL1/PD1 expression in MBC, as well as its correlation with prognosis. Methods A total of 60 patients diagnosed with MBC from January 2006 to December 2017 were included in our study. The percentage (%) and quantification (per mm(2)) of TILs and presence of tertiary lymphoid structures (TLS) were evaluated by hematoxylin and eosin staining (HE). The quantification of CD4+, CD8+ TILs (per mm(2)), and PD-1/PDL1 expression were evaluated through immunohistochemistry and analyzed in relation to clinicopathological characteristics. A >= 1% membranous or cytoplasmatic expression of PD1 and PDL1 was considered a positive expression. Results We found squamous cell carcinoma MBC (33/60, 55%) exhibiting most TILs of all the MBC subtypes (p = 0.043). Thirty-three of 60 (50%) of the patients had coexisting invasive ductal carcinoma of no special type (IDC-NST), and the average percentage of TILs in MBC components was lower compared with NST components (p < 0.001). Thirty (50%) patients exhibited positive (>= 1%) PDL1 expression in their tumor cells, while 36 (60%) had positive (>= 1%) PDL1 expression in their TILs. Twenty-seven (45%) of all the patients had positive (>= 1%) PD1 expression in their tumor cells and 33 (55%) had PD1-positive (>= 1%) stromal TILs. More CD8+ TILs were associated with positive PDL1 expression of tumor cells as well as positive PD1 expression in stromal cells. Greater number of stromal TILS (> 300/mm(2), 20%), CD4+ TILs (> 250/mm(2)), and CD8+ TILs (> 70/mm(2)) in MBC were found associated with longer disease-free survival. Positive expression of PDL1 in tumor cells (>= 1%) and PD1 in stromal cells (>= 1%) were also associated with longer survival. Conclusions The immune characteristics differ in various subtypes as well as components of MBC. Immune parameters are key predictive factors of MBC and provide the clinical significance of applying immune checkpoint therapies in patients with MBC.