鲍恩样丘疹病皮损中细胞周期调控蛋白表达与人乳头瘤病毒感染的研究

Relationship between the expressions of cell cycle regulatory proteins and human papillomavirus infection in bowenoid papulosis

目的探讨鲍恩样丘疹病（BP）皮损中人乳头瘤病毒（HPV）感染与细胞周期相关因子细胞周期蛋白D1（Cyclin D1）、细胞周期蛋白E（Cyclin E）及其依赖性蛋白激酶抑制蛋白p27表达的相关性。方法基因芯片法检测BP皮损组织中人乳头瘤病毒感染（HPV）类型，免疫组化方法检测44例BP皮损组织及10例正常包皮环切组织中细胞周期调控蛋白Cyclin D1、Cyclin E及p27的表达水平。结果44例BP中HPV感染率为100％，高危型感染38例，占86．36％，其中含HPVl6感染者30例，占68．18％，单一HPV16感染者16例，合并其他高低危混合感染者14例，其他高危型感染为8例，低危感染6例，主要为HPV6型感染。在BP组织中，HPV高危组（U=53．00，P〈0．05）、高低危混合组（U=12．00，P〈0．01），低危组（U=5．00，P〈0．01）中Cyclin D1表达较正常组显著增高，高低危混合组（U=44．00，P〈0．01）、低危组（U：22．50，P〈0．05）Cyclin D1表达较高危组显著增高；Cyclin E在HPV高危组（u=0．00，P〈0．01），高低危混合组（u=4．00，P〈0．01），低危组（U=1．50，P〈0．01）的表达显著高于正常组织，高危组显著高于低危组（u=11．00，P〈0．01）；p27的表达在HPV高低危感染中差异无统计学意义。p27在年龄〉50岁组较20～30岁组（U=47．00，P〈0．05）、31～50岁组（u=55．50，P〈0．05）显著增高。Cyclin E的表达在年龄〉50岁组较20～30岁组（u=45．50，P〈0．05）显著增高。还发现，女性患者Cyclin E的表达明显高于男性患者（u=137．50，P〈0．05）。结论不同HPV感染类型中，细胞周期调控蛋白CyclinD1、Cyclin E及p27的表达存在差异。

Objective To evaluate the relationship of human papillomavirus （HPV） infection with expressions of cell cycle regulatory proteins cyclin D1, E and their dependent kinase inhibitor p27 in bowenoid papulosis （BP）. Methods Tissue specimens were obtained from the lesions of 44 patients with BP, and circumcised foreskin tissue from 10 males served as the control. Gene chip was used to determine the genotypes of HPV, and immunohistochemistry to quantify the expressions of cyclin D1, E, p27, in these specimens. Results Of the 44 BP specimens, all were positive for HPV DNA, 38 （86.36%） for high risk types of HPV, and 6 for low risk types of HPV. Of the high risk HPV-positive specimens, 30 （68.18%） harbored HPV16, 16 harbored single HPV 16, 14 harbored other types of HPV besides HPV 16, 8 harbored other high risk types of HPV. HPV 6 predominated in low risk HPV-positive specimens. The expression of cyclin D1 was significantly higher in patients with high-risk HPV （u = 53.00, P〈 0.05）, with both high and low risk HPV （u = 5.00, P〈 0.01） and with low risk HPV （u = 22.50, P 〈 0.05） than in normal human controls, and higher in patients with both high and low risk HPV （u = 44.00, P〈 0.01） and with low risk HPV （u = 22.50, P〈 0.05） than those with high risk HPV. In the case of cyelin E expression, patients with high risk HPV （u = 0.00, P 〈 0.01 ）, with both high and low risk HPV （u = 4.00, P〈 0.01）, and with low risk HPV （u = 1.50, P〈 0.01） were higher than normal human controls, and patients with high risk HPV were higher than those with low risk HPV （u = 11.00, P 〈 0.01）. No significant difference was observed in the expression of p27 between patients with high and low risk types of HPV. A significant increase was observed in the expression of p27 in patients aged 〉 50 years compared with patients aged 20-30 years（u = 47.00, P 〈 0.05） and aged 31-50 years （u = 55.50, P 〈 0.05） , as well as in the expression of cyclin E in patients aged 〉 50 years compared with those aged 20-30 years （u = 45.50, P 〈 0.05）, and in female patients compared with male patients （u = 137.50, P 〈 0.05）. Conlusion There is a significant difference in the expression of cyclin D1, E and p27 among patients with BP infected with different types of HPV.