宫颈上皮内瘤变及宫颈鳞癌中DLK/ZIPK、Intβ_1的表达及意义

Expression and Clinical Significance of DLK/ZIPK and Integrinβ_1 in Cervical Intraepithelial Neoplasia and Cervical Cancer

目的探讨死亡相关蛋白样激酶(DLK/ZIPK)、整合素β1(Intβ1)在人宫颈上皮内瘤样变(CIN)及宫颈鳞癌(SCC)中的表达及意义。方法应用免疫组化SABC法检测15例正常宫颈上皮(NE)、30例CIN及85例SCC中DLK/ZIPK和Intβ1蛋白的表达情况,并分析两者与临床病理参数之间的关系。结果①在NE、CIN及SCC中,DLK/ZIPK的阳性率分别为93.3%、63.3%、32.9%,且DLK/ZIPK的低表达与宫颈癌的肿瘤大小、肌层浸润深度、细胞分化及淋巴结转移有关,与脉管浸润及患者年龄无关。②Intβ1在NE、CIN及SCC的阳性率分别为13.3%、63.3%、85.9%,Intβ1与宫颈癌的淋巴结转移及组织分化有关,与患者年龄、肿瘤大小肌层浸润深度及脉管浸润无关。③DLK/ZIPK与Intβ1在宫颈癌的发生发展过程中呈负相关(r=-0.244,P=0.024)。结论 DLK/ZIPK的表达下调及Intβ1的高表达与宫颈癌的发生发展过程密切相关,在宫颈鳞癌的发生发展中可能发挥协同作用。

Objective To investigate the expression of DAP-like kinase/zipper interacting protein kinase（DLK/ZIPK） and Integrinβ1 and its clinical significance in cervical intraepithelial neoplasia（CIN） and squamous cell carcinoma（SCC）.Methods Immunohistochemistry technique was used to study the expression of DLK/ZIPK and Integrinβ1 in 15cases of normal cervical epithelium（NE）,30 cases of CIN and 83 cases of SCC.The relationship between the clinicopathologic characteristics and DLK/ZIPK and Integrinβ1 was analyzed.Results ①The positive rate of DLK/ZIPK in NE was 93.3%,much higher than those 63.3% in CIN and 32.9% in SCC（P0.05）.DLK/ZIPK low expression was closely correlated with tumor size,depth of myometrial invasion,histopathologic grade,and lymph node metastasis（LNM）,but not with age and vessel invasion.②The positive rates of Integrinβ1 were 63.3 % in CIN and 85.9% in SCC,both higher than 13.3% in NE.Differences among them were statistically significant（P0.05）.Intβ1 high expression was closely correlated with LNM and histopathologic grade,but not with age,tumor size,depth of myometrial invasion and vessel invasion.③DLK /ZIPK and Intβ1 were negatively correlated in the process of development of cervical cancer.Conclusion Both low or absent expression of DLK/ZIPK and high expression of Integrinβ1 have cooperatively promoted the development of cervical cancer.