Prognostic Significance of Tumor-Infiltrating Lymphocytes and the Tertiary Lymphoid Structures in HER2-Positive Breast Cancer Treated With Adjuvant Trastuzumab.
曲妥珠单抗辅助性治疗的HER-2阳性乳腺癌肿瘤内淋巴细胞浸润及三级淋巴结构的预后意义
Lee HJ,Kim JY,Park IA,Song IH,Yu JH,Ahn JH,Gong G
Abstract
Tumor-infiltrating lymphocytes (TILs) have prognostic significance in breast cancer. The tertiary lymphoid structure (TLS) is related to the influx of TILs, and expression of major histocompatibility complex (MHC) I in tumor cells is necessary for the effective action of TILs.
We retrospectively evaluated the relationship of TILs and TLS and the expression of MHC I in 447 HER2-positive breast cancers treated with chemotherapy and 1 year of trastuzumab.
TILs were more abundant in hormone receptor (HR)-/HER2+ tumors than in HR+/HER2+ tumors. HR-/HER2+ breast cancers with abundant TILs showed a higher histologic grade, the absence of lymphovascular invasion, the presence of peritumoral lymphocytic infiltration, moderate to abundant TLSs in adjacent tissue, and stronger HLA-ABC and HLA-A expression. Abundant TILs and the absence of lymphovascular invasion were found to be good, independent prognostic factors for disease-free survival in patients with HR-/HER2+ breast cancer. The level of TILs was not associated with the patients' prognosis in HR+ tumors.
Abundant TILs are an independent prognostic factor in HR-/HER2+ breast cancers. Evaluation of TILs in HR-/HER2+ breast cancers may provide valuable information regarding the prognosis of patients treated using adjuvant chemotherapy and trastuzumab.
摘要
肿瘤内淋巴细胞浸润(TIL)在乳腺癌患者具有预后意义。三级淋巴结构(TLS)与TIL的淋巴细胞进入量有关,并且就TIL的有效反应活动而言,肿瘤细胞需要表达主要组织相容性复合体I(MHC-I)。我们回顾性评估了接受化疗以及1年曲妥珠单抗治疗的447例HER-2阳性乳腺癌患者TIL与TLS之间的关系以及MHC I的表达。与激素受体(HR)+/HER2+的肿瘤相比,TIL在HR-/HER2+肿瘤中更为丰富。HR-/HER2+、伴有丰富TIL的乳腺癌表现为更高组织级别、缺乏淋巴管血管浸润、肿瘤周围存在淋巴细胞浸润、肿瘤周边组织内可见中等至丰富的TLS、并且强阳性表达HLA-ABC 和 HLA-A。我们发现丰富的TIL和缺乏淋巴管血管浸润是评估HR-/HER2+乳腺癌患者无病生存的良好、独立预后因素。TIL水平与HR+肿瘤患者预后不相关。丰富的TIL是HR-/HER2+乳腺癌患者的一个独立的预后因素。对HR-/HER2+乳腺癌的TIL评估可以为进行辅助性化疗和曲妥珠单抗治疗的患者的预后提供有价值的信息。
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