Morohashi Satoko, Kusumi Tomomi, Sato Fuyuki, Odagiri Hiroki, Chiba Hiroki, Yoshihara Shuichi, Hakamada Kenichi, Sasaki Mutsuo, Kijima Hiroshi
Department of Pathology, Hirosaki University School of Medicine, Aomori 036-8562, Japan.
Int J Mol Med. 2007 Aug;20(2):139-43.
Claudins (CLDNs) constitute the major transmembrane proteins of tight junctions. It may be hypothesized that changes in or loss of expression of tight junctional proteins such as CLDNs can lead to cellular disorientation and detachment, which is commonly seen in neoplasia. Recent studies have suggested that claudin-1 (CLDN1) plays an important role in invasion and metastasis and claudin-4 (CLDN4) has a particular role in mammary glandular cell differentiation and carcinogenesis. In this study, we examined 83 breast cancer cases and demonstrated immunohistochemical expression patterns of CLDN1/CLDN4 in recurrent and non-recurrent groups. We found significant results between the recurrent and non-recurrent group for expression of CLDN1/CLDN4. The recurrent group (26 cases) showed decreased expression patterns of CLDN1 (p<0.001), compared to the non-recurrent group (57 cases). Decreased expression of CLDN1 (p<0.0001) correlated with short disease-free interval. The lymph node metastasis-positive group showed decreased expression patterns of CLDN1 (p=0.001). However, there was no significance between the recurrent group and non-recurrent group in CLDN4 expression. There was no significance between histological factors and CLDN4 expression. The results indicated that CLDN1 expression correlated with the recurrence status and malignant potential of breast cancer.
紧密连接蛋白（CLDNs）是紧密连接的主要跨膜蛋白。可以推测，紧密连接蛋白如CLDNs表达的改变或缺失会导致细胞定向紊乱和脱离，这在肿瘤形成中很常见。最近的研究表明，紧密连接蛋白-1（CLDN1）在侵袭和转移中起重要作用，而紧密连接蛋白-4（CLDN4）在乳腺细胞分化和致癌过程中具有特殊作用。在本研究中，我们检查了83例乳腺癌病例，并展示了CLDN1/CLDN4在复发组和非复发组中的免疫组化表达模式。我们发现复发组和非复发组在CLDN1/CLDN4表达上有显著差异。与非复发组（57例）相比，复发组（26例）的CLDN1表达模式降低（p<0.001）。CLDN1表达降低（p<0.0001）与无病生存期缩短相关。淋巴结转移阳性组的CLDNl表达模式降低（p=0.001）。然而，复发组和非复发组在CLDN4表达上没有显著差异。组织学因素与CLDN4表达之间也没有显著差异。结果表明，CLDN1表达与乳腺癌的复发状态和恶性潜能相关。
