Wnt/β-catenin信号活化与乳腺癌肿瘤浸润淋巴细胞的相关性及其临床意义

Objective: To study whether intratumoral Wnt/β-catenin signaling can affect lymphocyte infiltration in breast cancer and its clinical significance by taking cytoplasmic/nuclear accumulation of β-catenin as a marker of Wnt/β-catenin pathway activation. Methods: Retrospective analysis of 90 primary operable breast cancer specimens was made in this study. The distribution of stromal TILs was assessed by regular H-E staining. And the expression of β-catenin was assessed by immunohistochemical method on consecutive sections. The correlation between tumor β-catenin expression and lymphocyte infiltration was evaluated by statistical analysis. Results: Abnormal β-catenin expression was associated with tumor grade (P<0.05), ER expression (P<0.01), and PR expression (P<0.01). However, it had no correlation with patient age, tumor size, axillary lymph node metastasis, or tumor TNM stage. β-catenin expression was significantly upregulated in hormone receptor negative breast cancer subtypes, i.e. HER2-enriched BC and TNBC, compared to hormone receptor positive breast cancer subtypes (luminal A, B) (P<0.05). Furthermore, high levels of stromal TILs were associated with β-catenin overexpression by breast cancer (P<0.05). Higher stromal TILs infiltration was detected in hormone receptor negative breast cancer compared with hormone receptor positive one. Conclusion: Wnt/β-catenin signaling is significantly upregulated in hormone receptor negative breast cancer, and promotes lymphocyte infiltration to tumor stroma. Wnt/β-catenin pathway may play a critical role in anti-cancer immunity, particularly in hormone receptor negative breast cancer, and may serve as a potential target for regulating immune infiltrates in breast cancer.