Nucleocytoplasmic Localization of CXCL5 in Treatment-Na？ve Breast Carcinoma: A Novel Pattern Associated with Aggressive Clinicopathological Features

Background: Breast cancer is the most common malignancy in women and exhibits marked biological heterogeneity with variable clinical outcomes. Inflammatory chemokines, particularly CXCL5, contribute to tumor progression through activation of CXCR2 signaling, promoting proliferation, angiogenesis, epithelial–mesenchymal transition, and recruitment of tumor-associated neutrophils. While CXCL5 is primarily a secreted cytoplasmic protein, emerging evidence suggests that altered subcellular localization may reflect dysregulated signaling with potential biological and clinical implications. Objectives: To evaluate the immunohistochemical expression and subcellular localization of CXCL5 in treatment-na？ve breast cancer and to correlate its patterns with clinicopathological parameters. Patients and Methods: This retrospective study included 131 cases of treatment-na？ve invasive breast carcinoma of no special type. Formalin-fixed, paraffin-embedded tissue blocks were retrieved from the archives of the Pathology Department, Faculty of Medicine, Menoufia University (2018–2022). Clinicopathological data were obtained from medical records and pathology reports. Hematoxylin and eosin-stained sections were reviewed, and CXCL5 expression and localization were assessed by immunohistochemistry. Associations with clinicopathological variables were statistically analyzed. Results: CXCL5 expression was detected in 123 cases (93.9%), with cytoplasmic localization predominating (72.2%), while nucleocytoplasmic expression was observed in 19.8%. Nucleocytoplasmic localization was significantly associated with higher tumor grade, advanced T stage, increased nodal burden, distant metastasis, higher mitotic count, elevated proliferative index, poor Nottingham Prognostic Index, hormone receptor negativity, HER2 positivity, and aggressive molecular subtypes, particularly triple-negative tumors (all p < 0.01). Conclusion: Nucleocytoplasmic localization of CXCL5 represents a novel and clinically relevant expression pattern associated with aggressive tumor behavior, suggesting its potential role as a prognostic biomarker in treatment-na？ve breast cancer. ？