Comparison of claudin-3 and claudin-4 expression in bilateral and unilateral breast cancer

 Jolanta Szade, Michał Kunc, Beata Pieczyńska-Uziębło, Maciej Świerblewski, Wojciech Biernat, Jacek Jassem, Elżbieta Senkus

Abstract:

Claudins are essential components of tight junctions, which are frequently deregulated in breast cancer. The aim of the current study was to assess claudin-3 and -4 expression in bilateral breast cancer (BBC) and unilateral breast cancer (UBC). Immunohistochemical expression of claudin-3 and claudin-4 was evaluated in tissue microarrays containing 174 cases of BBCs paired with 174 cases of solitary tumors. Each case was classified as claudin-high or claudin-low depending on the H-score value. The results were correlated with histopathological features and the expression of basic breast cancer biomarkers. Median H-scores for claudin-3 were significantly higher in the synchronous BBC (sBBC) than in UBC. Claudin-4-high cases were more prevalent than within the whole BBC group, and sBBC and metachronous BBC (mBBC) alone. In the BBC group negative ER, high Ki-67 and high claudin-3 were independent factors correlated with high claudin-4. In the UBC group, Ki-67 >14% and high claudin-3 were associated with high claudin-4. Our study demonstrates that the expression of claudin-4 is significantly higher in UBC compared to BBC tumors. We also demonstrated that high claudin-4 expression in BBC is associated with a more aggressive phenotype (lack of steroid receptors, HER2 overexpression, and high Ki-67). It is possible that claudins down- and upregulation may depend on different triggers and lead to various consequences in UBC and BBC.