Cripto-1在子宫颈癌中的表达及临床意义

Expression and clinical significance of Cripto-1 in cervical carcinoma

目的检测Cripto-1在正常子宫颈(normal cervical epithelium,NCE)、子宫颈上皮内瘤变(cervical intraepithelial neopla-sia,CIN)、子宫颈浸润癌(invasive carcinoma of cervix,ICC)中的表达情况及其与疾病进展的关系。方法采用Western Blot、RT-PCR和免疫组化SP法检测26例ICC、52例CIN和20例NCE中Cripto-1的表达差异,结合临床病理参数进行分析。用免疫组化法检测子宫颈癌Caski细胞诱导分化前后Cripto-1的表达差异。结果 Western Blot检测显示Cripto-1蛋白在ICC中平均表达水平(0.92±0.68)明显高于CIN(0.31±0.23)和NCE(0.09±0.06)(P<0.05),而其在CIN中表达也较NCE高(P<0.05)。RT-PCR分析显示ICC中Cripto-1 mRNA平均表达水平(0.62±0.36)高于CIN(0.24±0.14)和NCE(0.10±0.09)(P<0.05),且CIN中Cripto-1 mRNA表达较NCE高(P<0.05)。免疫组化结果显示ICC中Cripto-1蛋白阳性表达率为57.7%(15/26),较CIN(26.9%)和NCE(5%)明显增高(P<0.05),CIN中Cripto-1蛋白阳性表达率较NCE中升高(P<0.05);Crip-to-1在子宫颈癌中的表达与患者年龄、组织学类型、病理分级、临床分期无关(P>0.05),与有无淋巴结转移有关(P<0.05)。诱导分化治疗后Caski细胞中Cripto-1蛋白表达较对照组明显降低。结论 Cripto-1可能在子宫颈癌的发生、发展中起着重要的作用,充当癌基因的角色;检测Cripto-1的表达可作为子宫颈癌及其癌前病变诊断的一项辅助指标,可成为一个肿瘤治疗的靶向。

Purpose To investigate the expression of Cripto-1 in normal cervical epithelium（NCE）,cervical intraepithelial neoplasia（CIN）,invasive carcinoma of cervix（ICC）,and its relation with progression of the disease.Methods Western Blot,RT-PCR and immunohistochemistry were used to examine the expression levels of Cripto-1 in 26 cases of cervical carcinoma,52 cases of cervical intraepithelial neoplasia and 20 cases of normal cervical epithelium.The association between expression of Cripto-1 with clinicopathologic parameters was assessed.Using immunohistochemical method,we examined Cripto-1 expression levels of Caski cells before and after treatment.Results Western Blot showed that the average expression level of Cripto-1 in ICC（0.92±0.68） was significantly higher than in CIN（0.31±0.23） and NCE（0.09±0.06）（P0.05）,and that in CIN was higher than in NCE（P0.05）.RT-PCR revealed the average expression level of Cripto-1 mRNA in ICC（0.62±0.36） was higher than in CIN（0.24±0.14） and NCE（0.10±0.09）（P0.05）,and that in CIN was higher than in NCE（P0.05）.The immunohistochemical staining displayed the positive expression rate in NCE was only 5%,but significantly higher in CIN（26.9%）and ICC（57.7%）（P0.05）.Cripto-1 protein expression in ICC was correlated to lymph node metastasis（P0.05）,but no correlation to patients＇ age,histological type,pathologic grade,and clinical stage.Cripto-1 expression obviously decreased in Caski cells after treatment.Conclusion The expression of Cripto-1 may play an important role in the carcinogenesis and development of cervical carcinoma,and could be used as a tumor marker for early diagnosis of cervical carcinoma and precancemns lesions,and it could become a target for cancer therapy.