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Microsatellite instability and mismatch repair protein expressions in lymphocyte‐predominant breast cancer

机译:微卫星不稳定性和淋巴细胞乳腺癌中的不匹配修复蛋白表达

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摘要

The frequency of microsatellite instability (MSI) is reportedly extremely low in breast cancer, despite widespread clinical expectations that many patients would be responsive to immune‐checkpoint inhibitors (ICI). Considering that some triple‐negative breast cancers (TNBC) responded well to ICI in a clinical trial and that a high density of tumor‐infiltrating lymphocytes (TILs) is frequently observed in other cancers with high levels of microsatellite instability (MSI‐H), we hypothesized that some TNBC with a high density of TILs would be MSI‐H. Medullary carcinoma (MedCa) of the breast, a rare histological type, is characterized by a high density of TILs. Considering that MedCa of the colon is often MSI‐H, we suspected that MedCa in breast cancer might also include MSI‐H tumors. Therefore, we conducted MSI tests on such breast cancers with a high density of TILs. The MSI status of 63 TIL‐high TNBC and 38 MedCa tumors, all from Asian women who had undergone curative surgery, were determined retrospectively. DNA mismatch repair (MMR) proteins and PD‐L1 expression were also investigated immunohistochemically. All samples were microsatellite stable, being negative for all microsatellite markers. TIL‐high TNBC with low MLH1 protein had higher levels of PD‐L1 in stromal immune cells (  = .041). MedCa tumors showed significantly higher PD‐L1 expression in immune cells than in TIL‐high TNBC (
机译:据报道,微卫星不稳定性(MSI)的频率在乳腺癌中非常低,尽管许多患者对免疫检查点抑制剂(ICI)响应的临床预期很大。考虑到一些三重阴性乳腺癌(TNBC)在临床试验中对ICI响应良好,并且在具有高水力疏水素不稳定性(MSI-H)的其他癌症中经常观察到高密度的肿瘤渗透淋巴细胞(TIL),我们假设具有高密度的TNBC是MSI-H。乳腺癌(Medca)的乳腺癌(Medca),一种罕见的组织学型,其特征在于直线密度。考虑到结肠的枸杞往往是MSI-H,我们怀疑乳腺癌中的Medca可能还包括MSI-H肿瘤。因此,我们对这种乳腺癌进行了MSI测试,具有高密度的直线。重新定位了63个TIL-HIGHTNBC和38个中医肿瘤的MSI状态,所有来自疗法手术的亚洲女性。还研究了DNA失配修复(MMR)蛋白质和PD-L1表达,免疫组化。所有样品都是微卫星稳定的,对所有微卫星标记产生负面。具有低MLH1蛋白的TIL高TNBC在基质免疫细胞中具有较高水平的PD-L1(= .041)。 Medca肿瘤在免疫细胞中显示出显着高于免疫细胞的表达明显,而不是Til-High TNBC(

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