宫颈病变组织中Vimentin、P16^(INK4A)、Smad4的定位、表达及其在EMT中的作用

Expression and positioning of vimentin,P16^(INK4A) and Smad4 in cervical cancer tissues and its role in epithelial-mesenchymal transition

目的观察Vimentin、P16INK4A和Smad4在宫颈癌及前期病变中的定位与表达水平,探讨其对宫颈癌细胞上皮—间质转化(EMT)的影响和可能机制。方法免疫组织化学染色方法检测30例慢性子宫颈炎、30例低级别宫颈上皮内瘤变(CIN)、30例高级别CIN和30例宫颈癌中Vimentin、P16INK4A和Smad4的表达水平和定位。结果 Vimentin、P16INK4A和Smad4在各宫颈病变组织中呈不同程度阳性表达,在细胞质和细胞核均可表达。宫颈癌组织Vimentin表达水平较慢性子宫颈炎、低级别CIN、高级别CIN高(P均<0.01)。慢性子宫颈炎组织中P16INK4A阴性表达,在CIN和宫颈癌组织中表达水平升高(P均<0.01)。慢性子宫颈炎组织中Smad4在细胞核与细胞质均高表达,低级别CIN、高级别CIN和宫颈癌组织中Smad4细胞核表达水平降低(P均<0.01)。Spearman相关分析显示,120例宫颈病变组织中Smad4核表达与P16INK4A核质表达均呈负相关(r分别为-0.274、-0.387,P均<0.01),Smad4核表达与Vimentin核表达亦呈负相关(r=-0.209,P<0.05),P16INK4A核质表达与Vimentin核表达均呈正相关(r分别为0.334、0.443,P均<0.01)。宫颈癌中Vimentin、P16INK4A和Smad4无论细胞核表达或细胞质表达均与宫颈癌的分化和年龄无相关关系(P均>0.05)。结论 Vimentin、P16INK4A和Smad4在各宫颈病变组织细胞质和细胞核中呈不同程度阳性表达。Vimentin核表达是反映宫颈癌细胞EMT的良好指标,P16INK4A核表达和Smad4核表达与宫颈癌细胞EMT密切相关。

Objective To observe the subcellular localization and expression of vimentin, P16INK4A and Smad4 in cervical cancer and precursor lesions, and to investigate its effect and possible mechanism in the epithelial-mesenchymal transition （EMT） of cervical cancer cells. Methods Immunohistochemistry was used to analyze the expression and localiza- tion of vimentin, P16INK4A and Smad4 in 30 cases of patients with chronic cervicitis, 30 cases of low-grade cervical intraepi- thelial neoplasia （ CIN）, 30 cases of high-grade CIN and 30 cases of cervical cancer. Results The expression of vimen- tin, P16INK4A and Smad4 was positive to a certain degree in all cervical lesions, both in the cytoplasm and nucleus. Vimen- tin expression in cervical cancer was higher than that in chronic cervicitis, low-grade CIN and high-grade CIN （ all P 〈 0.01 ）. P16INKgA was negatively expressed in chronic cervicitis and showed higher expression in CIN and cervical cancer （ all P 〈 0.01 ）. Smad4 in the nucleus and cytoplasm was highly expressed in chronic eervicitis tissues, Smad4 expression in the nuclear was reduced in low-grade CIN, high-grade CIN and cervical cancer （ all P 〈 0.01 ）. Spearman correlation analysis showed nuclear Smad4 expression was negatively correlated with the expression of nuclear and cytoplasmic P16JNK4A （ r = - 0. 274, - 0.387, all P 〈 0.01 ） , also negatively correlated with the expression of nuclear vimentin （ r = - 0. 209, P 〈0.05 ） , both P16INK4A expression in nucleus and cytoplasm was positively correlated with nuclear vimentin in 120 cases of cervical lesions（r =0.334, 0. 443, respectively; all P 〈0.01 ）. Neither the nuclear nor cytoplasmic expression of vimentin, P16INK4A and Smad4 had correlation with age and differentiation in cervical cancer （ all P 〉 0.05 ）. ConclusionsThe expression of vimentin, P16INK4A and Smad4 is positive in nucleus and cytoplasm with varying degrees in all cervical lesions. Nuclear vimentin is a remarkable indicator in EMT of cervical cancer cells. The nuclear expression of P16INK4A and Smadd is significantly associated with EMT of cervical cancer cells.