锌指蛋白A20和NF—κB在皮肤鳞状细胞癌的表达及其与人乳头状瘤病毒感染的关系

Expressions of zinc finger protein A20 and nuclear factor-κB in cutaneous squamous cell carcinoma tissue and their correlation with human papillomavirns infection

目的探讨皮肤鳞状细胞癌（皮肤鳞癌）组织中锌指蛋白A20、核因子κB（NF—κB）的表达及其与人乳头状瘤病毒（HPV）感染的关系。方法收集43例皮肤鳞状细胞癌和21例健康人皮肤组织，利用基因芯片法检测21种HPV亚型，免疫组化法检测锌指蛋白A20和NF—κB表达水平，分析临床病理特征及其与HPV感染的关系。结果锌指蛋白A20、NF—κB的表达水平在皮肤鳞癌患者不同年龄、性别、肿瘤原发部位和组织学分级组间差异均无统计学意义（P〉0．05）；皮肤鳞癌临床不同分期组问锌指蛋白A20、NF—κB的表达水平（I＋Ⅱ级组39例和Ⅲ级组4例锌指蛋白A20分别为25．85±3．84和48．34±7．69，NF—κB分别为46．64±8．93和57．34±10．02）以及有无淋巴结转移组间（有转移组3例和无转移组40例锌指蛋白A20分别为35．34±6．02和26．51±4．09，NF—κB分别为57．53±13．32和45．45±9．64）差异均有统计学意义（P〈0．05或〈0．01）。在低危型HPV、高危型HPV、高危型／f氐危型混合感染的皮肤鳞癌组织中，A20表达分别为8例中2例、13例中5例和3例中1例阳性，NF—κBp65表达分别为3、10和2例阳性，经Fisher精确概率法计算，NF—κBp65与A20在3组中表达的阳性率差异均无统计学意义（P〉0．05）。HPV感染的鳞癌组织中锌指蛋白A20和NF—κBp65染色积分呈显著正相关（r=3．14，P〈0．05）。结论A20与NF—κB高表达在HPV感染致皮肤鳞癌形成过程中发挥了重要的作用。

Objective To measure the expressions of zinc finger protein A20 and nuclear factor （NF）-κB in cutaneous squamous cell carcinoma （CSCC） tissue and their correlation with human papillomavirus （HPV） infection. Methods Tissue specimens were obtained from the lesions of 43 patients with CSCC and normal skin of 21 healthy human controls. Gene chips were used to detect the DNA of 21 HPV subtypes in these specimens. The expression levels of zinc finger protein A20 and NF-κB were determined by immunohistochemistry. The correlation between clinicopathological features of CSCC and HPV infection was estimated by Spearman rank correlation analysis. Results No significant difference was found in the expression level of either zinc finger protein A20 or NF-κB among patients of different age groups, gender, and with CSCC of different primary sites or histological grade （all P 〉 0.05）. However, there was a significant difference in the expression levels of zinc finger protein A20 and NF-κB between 39 patients with histological grade I or Ⅱ and 4 patients with grade m （25.85 ± 3.84 vs. 48.34± 7.69 for zinc finger protein A20, 46.64 ± 8.93 vs. 57.34 ± 10.02 for NF-κB, both P 〈 0.05）, and between 3 patients with nodular metastasis and 40 patients without （35.34 ± 6.02 vs. 26.51 ±4.09 for zinc finger protein A20, 57.53 ± 13.32 vs. 45.45 ± 9.64 for NF-κB, P 〈 0.05 or 0.01 ）. The expression rate was 2/8, 5/13 and 1/3 for zinc finger protein A20 （P 〉 0.05）, 3/8, 10/13 and 2/3 for NF-κB （P 〉 0.05）, in CSCC tissue specimens infected with low-risk HPV subtypes, high-risk subtypes, concurrent low- and high-risk HPV subtypes respectively. In HPV-infected CSCC tissue, a significantly positive correlation was found between the staining scores for zinc finger protein A20 and for NF-κB p65（r = 3.14, P 〈 0.05）. Conclusion The high expressions of NF-κB and zinc finger protein A20 may play an important role in the oncogenesis of CSCC induced by HPV infection.