Impact of chemotherapy on the expression of claudins and cadherins in invasive breast cancer.

ABSTRACT

The importance of the expression profile of claudins in the molecular classification of breast cancer (BC) is currently under investigation. Claudins, together with cadherins, serve an important role in the epithelial-mesenchymal transition and influence the chemosensitivity of cancer cells. Adjuvant chemotherapy is administered following surgical resection in selected cases of BC. Previous neoadjuvant chemotherapy may change the molecular profile of a tumour and subsequently also its chemosensitivity. In the current study, the expression of claudin-1, -3 and -4, E- and N-cadherin and the standard BC biomarkers [oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and marker of proliferation Ki-67 (Ki-67)] in formalin-fixed, paraffin-embedded sections from 62 patients with invasive BC was analysed using immunohistochemistry prior to and following neoadjuvant chemotherapy. The results revealed increased expression of claudin-1 (P=0.03) and decreased expression of claudin-3 (P=0.005), PR (P<0.001) and Ki-67 (P=0.01) following the neoadjuvant therapy. No significant changes in the expression of ER, claudin-4 or E- and N-cadherin were observed following therapy. Furthermore, an association between the expression of claudin-1 and the standard BC markers (P<0.05) was identified. A high expression of claudin-1 was more frequently observed in the triple-negative BC cohort than in the cohort with positive ER, PR and/or HER2 before (P=0.04) and after chemotherapy (P=0.02). The expression of N-cadherin was associated with the expression of ER, PR, HER2 and tumour grade (P<0.05). A positive association between the expression of claudin-3 and E-cadherin (P=0.005) was observed. No association was found between the expression of E- and N-cadherin. In conclusion, significant changes in the expression of claudin-1 and -3 but not in the expression of claudin-4, E- and N-cadherin were observed in samples taken from patients with BC following chemotherapy. These findings indicate that claudins-1 and -3 serve a role in the response of BC to chemotherapy.