Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Pathol Int. 2010 Oct;60(10):673-80. doi: 10.1111/j.1440-1827.2010.02587.x. Epub 2010 Aug 17.
Claudin-18 plays a key role in constructing tight junctions, and altered claudin-18 expression has been documented in various human malignancies; however, little is known about the biological significance of claudin-18 in colorectal cancer (CRC). The aim of this study is to investigate the significance of claudin-18 expression in CRC and its association with clinicopathological factors. We performed clinicopathological analysis of claudin-18 expression in a total of 569 CRCs by immunohistochemistry. Moreover, we investigated the association between claudin-18 and various markers including gastric/intestinal phenotype (MUC5AC, MUC6, MUC2 and CD10), CDX2, claudin-3, claudin-4, p53 and Ki-67. Claudin-18 expression was detected in 21 of the 569 CRCs (4%) and was seen exclusively on the cell membrane. Positive expression of claudin-18 showed a significant correlation with positive expression of MUC5AC (P < 0.0001) and negative expression of CDX2 (P= 0.0013). The prognosis of patients with positive claudin-18 expression was significantly poorer than in negative cases (P= 0.0106). Multivariate analysis revealed that T grade, M grade and claudin-18 expression were independent predictors of survival in patients with CRC. We revealed that claudin-18 expression correlates with poor survival in patients with CRC and is associated with the gastric phenotype.
紧密连接的形成中 Claudin-18 发挥着关键作用，在各种人类恶性肿瘤中已记录到 Claudin-18 表达的改变；然而，Claudin-18 在结直肠癌（CRC）中的生物学意义知之甚少。本研究旨在探讨 Claudin-18 在 CRC 中的表达意义及其与临床病理因素的关系。我们通过免疫组织化学法对总共 569 例 CRC 中 Claudin-18 的表达进行了临床病理分析。此外，我们还研究了 Claudin-18 与各种标志物（包括胃/肠表型标志物（MUC5AC、MUC6、MUC2 和 CD10）、CDX2、Claudin-3、Claudin-4、p53 和 Ki-67）之间的关联。在 569 例 CRC 中，有 21 例（4%）检测到 Claudin-18 表达，并且仅在细胞膜上检测到 Claudin-18 的阳性表达。Claudin-18 的阳性表达与 MUC5AC 的阳性表达（P < 0.0001）和 CDX2 的阴性表达（P = 0.0013）显著相关。Claudin-18 阳性表达患者的预后明显比阴性病例差（P = 0.0106）。多变量分析显示，T 分级、M 分级和 Claudin-18 表达是 CRC 患者生存的独立预测因素。我们揭示了 Claudin-18 表达与 CRC 患者的不良生存相关，并且与胃表型相关。
