Kojima Manabu, Sugimoto Kotaro, Tanaka Mizuko, Endo Yuta, Kato Hitomi, Honda Tsuyoshi, Furukawa Shigenori, Nishiyama Hiroshi, Watanabe Takafumi, Soeda Shu, Fujimori Keiya, Chiba Hideki
Department of Basic Pathology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
Department of Obstetrics and Gynecology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
Cancers (Basel). 2020 Sep 24;12(10):2748. doi: 10.3390/cancers12102748.
Among the claudin (CLDN) family, CLDN6 exhibits aberrant expression in various cancers, but its biological relevance has not yet been established. We generated a monoclonal antibody (mAb) against human CLDN6 and verified its specificity. By immunohistochemical staining and semi-quantification, we evaluated the relationship between CLDN6 expression and clinicopathological parameters in tissues from 173 cases of endometrial cancer.
The established mAb selectively recognized CLDN6 protein. Ten of the 173 cases (5.8%) showed high CLDN6 expression (score 3+), whereas 19 (11.0%), 18 (10.4%) and 126 (72.4%) cases revealed low CLDN6 expression (score 2+, 1+ and 0, respectively). In addition, intratumor heterogeneity of CLDN6 expression was observed even in the cases with high CLDN6 expression. The 5-year survival rates in the high and low CLDN6 groups was approximately 30% and 90%, respectively. Among the clinicopathological factors, the high CLDN6 expression was significantly associated with surgical stage III/IV, histological grade 3, lymphovascular space involvement, lymph node metastasis and distant metastasis. Furthermore, the high CLDN6 expression was an independent prognostic marker for overall survival of endometrial cancer patients (hazard ratio 3.50, = 0.014).
It can be concluded that aberrant CLDN6 expression is useful to predict poor outcome for endometrial cancer and might be a promising therapeutic target.
在紧密连接蛋白(CLDN)家族中,CLDN6在多种癌症中表现出异常表达,但其生物学相关性尚未明确。我们制备了一种针对人CLDN6的单克隆抗体(mAb)并验证了其特异性。通过免疫组织化学染色和半定量分析,我们评估了173例子宫内膜癌组织中CLDN6表达与临床病理参数之间的关系。
所制备的单克隆抗体可选择性识别CLDN6蛋白。173例病例中有10例(5.8%)显示CLDN6高表达(评分3+),而19例(11.0%)、18例(10.4%)和126例(72.4%)病例显示CLDN6低表达(分别为评分2+、1+和0)。此外,即使在CLDN6高表达的病例中也观察到了CLDN6表达的肿瘤内异质性。CLDN6高表达组和低表达组的5年生存率分别约为30%和90%。在临床病理因素中,CLDN6高表达与手术分期III/IV、组织学分级3级、淋巴血管间隙浸润、淋巴结转移和远处转移显著相关。此外,CLDN6高表达是子宫内膜癌患者总生存的独立预后标志物(风险比3.50,P = 0.014)。
可以得出结论,CLDN6异常表达有助于预测子宫内膜癌的不良预后,可能是一个有前景的治疗靶点。