HPV16E7、Cyclin D1和pRb的异常表达对喉癌的影响及其机制  

Effect and Mechanism of Abnormal Expressions of HPV16E7,Cyclin D1 and pRb on Laryngeal Carcinoma Tissues of Patients

作　　者：曾汉荣[1] 杨虹女 李文星[2] 涂欣[3] 李志华[2] 孔维佳[3] 

机构地区：[1]湖北省枝江市人民医院耳鼻咽喉科,湖北枝江443200 [2]武汉大学人民医院耳鼻咽喉-头颈外科,湖北武汉430060 [3]华中科技大学同济医学院附属协和医院耳鼻咽喉科,湖北武汉430022

出　　处：《武汉大学学报（医学版）》2016年第6期888-893,共6页Medical Journal of Wuhan University

基　　金：国家科技支撑计划资助项目(编号:201113AI11B12)

摘　　要：目的:探讨人乳头状瘤病毒16E7蛋白(HPV16E7)、细胞周期调节蛋白D1(Cyclin D1)和视网膜母细胞瘤蛋白(pRb)的异常表达对喉癌的影响及其机制。方法:取喉癌组织标本(喉癌组)、喉声带息肉组织标本(息肉组)和喉癌前病变组织标本(癌前组)各69例。采用过氧化物酶标记的链酶卵蛋白素染色免疫组织化学技术和Western Blot技术检测各组喉组织标本中HPV16E7、Cyclin D1和pRb的表达水平。结果:喉癌组HPV16E7和Cyclin D1阳性表达出现于细胞核,为大量黄褐色粗大颗粒,其阳性表达率分别为44.93%和52.17%,明显强于息肉组(分别为2.90%和8.70%)和癌前组(分别为10.14%和18.84%)(P均<0.01)。pRb的阳性表达发生于细胞核,为少而小的黄色颗粒,其阳性表达率为10.14%,显著小于息肉组的92.75%和癌前组的59.42%(P均<0.01)。癌前组HPV16E7和Cyclin D1阳性表达率较息肉组提高,pRb阳性表达率较息肉组明显下降(P均<0.005)。在喉癌肿瘤临床分期中,HPV16E7阳性表达率在Ⅰ-Ⅳ期中随着分期增加呈上升趋势,与临床Ⅲ期比较,HPV16E7在Ⅳ期的阳性表达率显著加重(P<0.025);Cyclin D1阳性表达率逐渐增多,pRb阳性表达率逐渐减少(P均<0.005)。在喉癌组织病理分级中,HPV16E7、Cyclin D1和pRb的阳性表达率随着分化程度减弱,HPV16E7和Cyclin D1阳性表达率分别为Ⅲ级>Ⅱ级>Ⅰ级,pRb阳性表达率为Ⅲ级<Ⅱ级<Ⅰ级(P均<0.005)。喉癌组中HPV16E7和Cyclin D1蛋白量均强烈增加,pRb蛋白定量显著减小;HPV16E7阳性表达率的增加与Cyclin D1阳性表达率增加呈显著的正相关(r=0.48,P<0.001),与pRb阳性表达率下降呈严重的负相关(r=-0.41,P<0.005);而Cyclin D1的阳性表达率增加与pRb阳性表达率下降也呈明显的负相关(r=-0.44,P<0.002)。结论:喉癌肿瘤的发生和发展与HPV严重感染宿主细胞造成HPV16E7过度表达,并刺激Cyclin D1恶性增加和pRb严重降低密切相关。通过对HPV16E7、Cyclin D1和pRb的检测有利于提�Objective：To explore the effect and mechanism of abnormal expressions of human papillomavirus 16E7protein（HPV16E7）,cell cycle protein D1（Cyclin D1）and retinoblastoma protein（pRb）on laryngeal carcinoma tissues of patients.Methods：All pathological specimens,from 69 cases of laryngeal carcinoma lesions（LCL group）,69 case of vocal cord polyp（VCP group）and69case of laryngeal precarcinoma lesions（LPL group）.The expression levels and clinical pathological features of HPV16E7,Cyclin D1 and pRb were detected by using the imunohistochemical SP staining and Western Blot methods.Results：The positive expressions of HPV16E7 and Cyclin D1 by immunohistochemical detection appeared in cell nuclei with a great number of thick and brown particles in LCL group.Compared with VCP and LPL groups,the positive expression percentage（PEP）of HPV16E7 and Cyclin D1 increased significantly in LCL group（44.93% vs 2.90% and 10.14%,52.17%vs 8.70%and 18.84%）（Pof all0.01）.The positive expression of pRb with a small number of little yellow particles also appeared in cell nuclei in LCL group.And its PEP decreased severely from 92.75%in VCP group and 59.42%in LPL group to 10.14%in LCL group（Pof all0.01）.Compared with VCP group,the PEP of HPV16E7 and Cyclin D1 in LPV group increased significantly,and the PEP of pRb decreased markedly in LPL group（P〈0.005）.According to the clinical stage in LCL group,the PEP of HPV16E7 was on the rise from stageⅠto stageⅣ,but it was not obviously different from stageⅠto stage Ⅲ（P〉0.10）.And It was only much more increased in stageⅣ,compared with stageⅢ（P〈0.025）.The PEPs of Cyclin D1 and pRb were significantly different from stageⅠto stage Ⅳ,which obviously increased for Cyclin D1 and decreased for pRb（Pof all〈0.005）.With the pathological degree in LCL group,the PEPs of HPV16E7,Cyclin D1 and pRb were significantly different with organization differentiation attenuating from degreeⅠto degreeⅢ.But the PEPs of HPV16E7 and Cyclin D1 were

关 键 词：喉癌组织 人乳头状瘤病毒16E7蛋白 细胞周期调节蛋白D1 视网膜母细胞瘤蛋白 

分 类 号：R767.19[医药卫生—耳鼻咽喉科] R739.65[医药卫生—临床医学]