CLEC3B (tetranectin) expression is associated with vascular localization and tumor aggressiveness in breast cancer.

Background: C-type lectin domain family 3 member B (CLEC3B), also known as tetranectin, is a secreted protein associated with extracellular matrix remodeling and tumor microenvironment regulation. However, its expression pattern and clinical significance in breast cancer tissues remain unclear. This study aimed to investigate CLEC3B expression in breast cancer tissues and its associations with clinicopathological characteristics and the tumor microenvironment. Methods: Ninety-eight women with newly diagnosed breast cancer who underwent surgical treatment at our hospital between September 2023 and December 2024 were included in this study. Tumor and adjacent non-tumorous tissues, including vascular regions, were obtained from the enrolled patients and processed for immunohistochemical analysis. CLEC3B expression was semiquantitatively graded from 1 to 4. Associations between CLEC3B expression, clinicopathological and biochemical variables were analyzed using the chi-square test, Spearman correlation, and multivariable logistic regression. Double immunofluorescence staining was performed to assess colocalization of CLEC3B with CD68 (macrophages) and CD31 (endothelial cells). Results: The expression of CLEC3B was identified in both tumor cell membrane and cytoplasm, and was significantly higher in breast cancer tissues than in adjacent non-tumorous tissues. CLEC3B expression was also significantly higher in blood vessels than in tumor parenchyma (p < 0.0001), indicating predominant vascular localization. High CLEC3B expression (grade 3-4) was associated with a tumor size of 2-5 cm, Ki-67 ≥14%, and the luminal B HER2-positive subtype. Spearman analysis showed that a high CLEC3B expression was correlated with larger tumor size, higher Ki-67 index, higher carcinoembryonic antigen level, and shorter prothrombin time. Multivariable logistic regression analysis further demonstrated that tumor size ≥2 cm and high Ki-67 (≥14%) were independently associated with high CLEC3B expression, whereas molecular subtype was not. CLEC3B was colocalized with CD68 and CD31, confirming its expression in macrophages and endothelial cells. CD4⁺ and CD8⁺ T-cell infiltration was abundant regardless of CLEC3B expression level. Conclusion: The expression of CLEC3B was upregulated in breast cancer tissues and predominantly localized to the tumor vasculature and macrophages. Its expression was associated with aggressive clinicopathological features and certain biochemical parameters. No apparent differences in CD4⁺ or CD8⁺ T-cell infiltration were observed across different levels of CLEC3B expression. These findings suggest that CLEC3B expression may be associated with vascular and microenvironment-related characteristics of breast cancer.