Detection of Increased Expression of Claudin-1 in Triple-Negative Breast Cancer: Analysis and Clinical-Pathological Correlation

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Abstract
Background Triple-negative breast cancer (TNBC) is a highly aggressive disease that lacks therapeutic targets and prognostic biomarkers. Claudin-1 is a well-described tight junction protein with prognostic value in many human cancers. Aims The need for the discovery of biomarkers of TNBC disease was a major reason for this study. Claudin-1 is a tight junction protein that has shown promising results in the prognosis and management of cancer in general. In the breast, claudin-1 expression and significance have shown variable results, especially in TNBC patients. Our study assessed expression of claudin-1 in a group of TNBC patients, and correlated this expression with clinical-pathological parameters, and with the expression of β-catenin. Materials and methods Tissues from a group of 52 TNBC patients were retrieved from the archives of the community hospital. All related information including demographical, pathologic and clinical data were retrieved. Immunohistochemistry assays of a rabbit polyclonal antibody anti-human claudin-1 were applied using the avidin-biotin peroxidase methodology. Results A statistically significant majority of TNBC cases positively expressed claudin-1 (81%, χ2=13.705; p<0.001). Most TNBC cases had grade 2 β-catenin expression (77.5%; p<0.001), and positive expression for claudin-1 correlated with that of β-catenin (χ2= 23.757; p<0.001). Claudin-1 and β-catenin expressions within tumour cells shared several features including absent or weakness of membranous expression, and redistribution of both proteins to the cytoplasm of tumour cells, and in some cases to the nuclei of these cells. Claudin-1 expression also correlates with adverse survival outcomes, where only four of 20 claudin-1-positive patients who received neo-adjuvant chemotherapy (NAC) achieved pathological complete response (pCR). Conclusions The above presents a complex role of claudin-1 in TNBC patients. In this study, claudin-1 expression was associated with poor prognostic features including invasion, metastases and adverse clinical outcomes. Claudin-1 expression in TNBC correlated with the expression of β-catenin, an important oncogene and a major contributor to the epithelial mesenchymal transition (EMT) phenomenon. Overall, the above results may serve as an impetus for further mechanistic studies to assess the exact role of claudin-1 in TNBC and its possible use in the management of this subset of breast cancer.

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