子宫颈鳞状细胞癌中△Np63α、DPC4/Smad4和P21的表达及其临床意义

Expressions of ΔNp63α, DPC4/Smad4 and P21 in cervical squamous cell carcinoma and their clinical significance

目的研究△Np63α、DPC4/Smad4和P21在子宫颈鳞状细胞癌中的表达情况。方法采用免疫组织化学ElivisionTMPlus法检测100例子宫颈鳞状细胞癌组织、40例子宫颈上皮内瘤变(CIN)和40例正常子宫颈组织中△Np63α、DPC4/Smad4和P21蛋白的表达情况。分析三者在子宫颈鳞状细胞癌的发生发展中的相互作用,及其与子宫颈鳞状细胞癌发生、发展和预后的关系。结果从正常子宫颈组织到子宫颈上皮内瘤变及子宫颈鳞状细胞癌,△Np63α和DPC4/Smad4的表达逐渐下降,P21的表达逐渐升高,差异有统计学意义(P<0.01);同时,三者的表达均与肿瘤的分化程度、临床分期和淋巴结转移有关(P<0.01)。另外,△Np63α与DPC4/Smad4的表达呈正相关关系(r=0.581,P<0.05);而DPC4/Smad4和△Np63α的表达与P21的表达均成负相关(r=-0.449,r=-0.254,P均<0.05)。同时,生存分析显示:△Np63α和DPC4/Smad4阳性表达组5年生存率显著高于其阴性表达组,差异有显著性(P<0.001);而P21阳性表达组则显著低于阴性表达组,差异有显著性(P<0.05)。结论△Np63α、DPC4/Smad4和P21的表达与子宫颈癌组织的发生发展、转移和预后等均有关;联合检测三者的表达情况,对子宫颈鳞状细胞癌的进展及预后判断有重要意义。

Objective To investigate the expressions of ΔNp63α, DPC4/Smad4 and P21 in cervical squamous cell carcinomas and explore their implications in tumorigenesis, progression and prognosis of the malignancy. Methods The expressions ofΔNp63α, DPC4/Smad4 and P21 were examined with immunohistochemistry in 100 specimens of cervical squamous cell carcinoma, 40 specimens of cervical intraepithelial neoplasia（CIN） and 40 specimens of normal cervical tissues to explore their associations with the occurrence, progression and prognosis of cervical squamous cell carcinoma. Results The expressions ofΔNp63α and DPC4/Smad4 decreased and P21 expression increased significantly in the order of normal cervical tissue, CIN and cervical squamous cell carcinoma（P〈0.01）, and their expressions were associated with the differentiation, clinical stages and lymph node metastasis of cervical squamous cell carcinoma（P〈0.01）. The expression of ΔNp63α was positively correlated with the expression of DPC4/Smad4（r=0.581, P〈0.05）, and they were both negatively correlated with P21 expression（r=-0.449 and-0.254, respectively; P〈0.05）. Kaplan-Meier survival analysis showed that patients with cervical squamous cell carcinoma positive for ΔNp63α and DPC4/Smad4 had a significantly higher 5-year survival rate than those negative for ΔNp63α and DPC4/Smad4（P0.001）; the patients positive for P21 had a significantly lower 5-year survival rate than the P21-negative patients（P0.005）. Conclusions The expressions of ΔNp63α, DPC4/Smad4 and P21 are related with the differentiation,invasion, lymph node metastasis, p TNM stage and prognosis of in cervical squamous cell carcinomas, suggesting their value as potential markers for prognostic evaluation of patients with cervical squamous cell carcinoma.