宫颈病变中人乳头瘤病毒来源E7蛋白表达及意义研究
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摘要
目的探讨宫颈病变中人乳头瘤病毒(HPV)来源的E7蛋白表达及其与临床诊断病理级别的相关性。方法选取北京大学第一医院2015—2018年收治的宫颈上皮内瘤变(CIN)及宫颈鳞癌患者133例,另选取同期宫颈组织病理结果正常的34例患者为阴性对照。采用免疫组化染色技术检测E7蛋白的细胞表达情况,并与宫颈癌高危型HPV感染替代性标志物p16蛋白做比较。结果 E7蛋白在低度鳞状上皮内病变(LSIL)即CINⅠ中阳性率为63.64%(14/22),而在高度鳞状上皮内病变(HSIL)即CINⅡ、Ⅲ病例中阳性率为91.84%(45/49)和98.18%(54/55),宫颈癌中阳性率为100%(7/7)。p16蛋白阳性率在CINⅠ中为59.09%(13/22),CINⅡ、Ⅲ中分别为93.88%(46/49)和96.36%(53/55)。两者检测结果高度相关(P<0.05)。随着宫颈病变程度的增加,E7和p16蛋白的阳性率均显著升高。但E7蛋白表达为片灶状阳性,与p16蛋白的弥漫阳性不同;同时HPV E7蛋白表达水平随CIN级别提升也显著增强。在HSIL及宫颈鳞癌中,E7蛋白阳性强度明显高于LSIL。随着患者年龄增长,E7蛋白的阳性率也呈升高趋势,并且其染色强度也增强。结论 E7癌蛋白的阳性率及其表达强度与宫颈病变程度密切相关,并与年龄有关;E7蛋白有望作为宫颈病变CIN诊断与分级的重要参考指标。
Objective To explore the expression of human papillomavirus(HPV)-derived E7 protein in cervical lesions[cervical intraepithelial neoplasia(CIN)and squamous carcinoma of the cervix(SCC)],and analyze the correlation in clinical diagnosis of pathological grades of cervical lesions.Methods A total of 133 cases were included,who suffered from CIN or SCC and were treated in Peking University First Hospital from 2015 to 2018,and 34 cases of normal cervical tissue were also included in the study as negative controls.The expression of E7 protein in tissue specimens was detected by immunohistochemistry(IHC).The expression profiles were compared with the surrogate marker p16 protein.Results Positive expression of E7 protein was 63.64%(14/22)in CINⅠ,and 91.84% and 98.18%(45/49,54/55)in CINⅡand CIN Ⅲ,and 100%(7/7)in SCC,respectively.Positive expression of P16 protein in CINⅠ,CINⅡ,CIN Ⅲand SCC was 59.09%(13/22),93.88%(46/49),96.36%(53/55)and 100%(7/7).With the increasing severity of cervical lesions,the intensities of E7 and p16 protein expression were significantly increased.However,the patterns of E7 protein expression showed generally as focal lesions in the epithelial layers of the CIN lesions,whereas the p16 expression often showed in a more diffused pattern.The level of E7 protein expression significantly increased with severity of CIN grades.In HSIL and SCC,the intensities of positive E7 protein expression were significantly higher than that of LSIL.Analysis of E7 protein expression in different age groups also revealed a correlation of increased E7 protein expression with older age,and the intensity of staining was also higher.Conclusion The positive rate and the expression intensity of E7 protein are closely related to the degress of cervical lesions and the age.E7 protein is expected to be used as a tumor biomarker for the clinical utility of diagnosis and grading cervical cancer SCC and its precursor CIN lesions.
Objective To explore the expression of human papillomavirus(HPV)-derived E7 protein in cervical lesions[cervical intraepithelial neoplasia(CIN)and squamous carcinoma of the cervix(SCC)],and analyze the correlation in clinical diagnosis of pathological grades of cervical lesions.Methods A total of 133 cases were included,who suffered from CIN or SCC and were treated in Peking University First Hospital from 2015 to 2018,and 34 cases of normal cervical tissue were also included in the study as negative controls.The expression of E7 protein in tissue specimens was detected by immunohistochemistry(IHC).The expression profiles were compared with the surrogate marker p16 protein.Results Positive expression of E7 protein was 63.64%(14/22)in CINⅠ,and 91.84% and 98.18%(45/49,54/55)in CINⅡand CIN Ⅲ,and 100%(7/7)in SCC,respectively.Positive expression of P16 protein in CINⅠ,CINⅡ,CIN Ⅲand SCC was 59.09%(13/22),93.88%(46/49),96.36%(53/55)and 100%(7/7).With the increasing severity of cervical lesions,the intensities of E7 and p16 protein expression were significantly increased.However,the patterns of E7 protein expression showed generally as focal lesions in the epithelial layers of the CIN lesions,whereas the p16 expression often showed in a more diffused pattern.The level of E7 protein expression significantly increased with severity of CIN grades.In HSIL and SCC,the intensities of positive E7 protein expression were significantly higher than that of LSIL.Analysis of E7 protein expression in different age groups also revealed a correlation of increased E7 protein expression with older age,and the intensity of staining was also higher.Conclusion The positive rate and the expression intensity of E7 protein are closely related to the degress of cervical lesions and the age.E7 protein is expected to be used as a tumor biomarker for the clinical utility of diagnosis and grading cervical cancer SCC and its precursor CIN lesions.
引文
[1]Narisawa-Saito M,Kiyono T.Basic mechanisms of high-risk human papillomavirus-induced carcinogenesis:roles of E6 and E7proteins[J].Cancer Sci,2007,98(10):1505-1511.
[2]Fiedler M,Muller-Holzner E,Viertler HP,et al.High level HPV-16 E7 oncoprotein expression correlates with reduced p Rb-levels in cervical biopsies[J].FASEB J,2004,18(10):1120-1122.
[3]Kaiser A,Jenewein B,Pircher H,et al.Analysis of human papillomavirus E7 protein status in C-33A cervical cancer cells[J].Virus Genes,2015,50(1):12-21.
[4]Whitehead M,Ohlschlager P,Almajhdi FN,et al.Human papillomavirus(HPV)type 16 E7 protein bodies cause tumour regression in mice[J].BMC Cancer,2014,14:367.
[5]Jabbar SF,Park S,Schweizer J,et al.Cervical cancers require the continuous expression of the human papillomavirus type 16E7 oncoprotein even in the presence of the viral E6 oncoprotein[J].Cancer Res,2012,72(16):4008-4016.
[6]Pinto AP,Degen M,Villa LL,et al.Immunomarkers in gynecologic cytology:the search for the ideal'biomolecular Papanicolaou test'[J].Acta Cytol,2012,56(2):109-121.
[7]Jaiswal N,John R,Chand V,et al.Oncogenic human papillomavirus 16E7 modulates SUMOylation of Fox M1b[J].Int J Biochem Cell Biol,2015,58:28-36.
[8]Bodily JM,Mehta KP,Laimins LA.Human papillomavirus E7enhances hypoxia-inducible factor 1-mediated transcription by inhibiting binding of histone deacetylases[J].Cancer Res,2011,71(3):1187-1195.
[9]Woodman CB,Collins SI,Young LS.The natural history of cervical HPV infection:unresolved issues[J].Nat Rev Cancer,2007,7(1):11-22.
[10]宋丹,孔为民,张同庆,等.宫颈癌治疗后高危型人乳头瘤病毒转阴与预后关系研究[J].中国实用妇科与产科杂志,2017,33(9):975-978.
[2]Fiedler M,Muller-Holzner E,Viertler HP,et al.High level HPV-16 E7 oncoprotein expression correlates with reduced p Rb-levels in cervical biopsies[J].FASEB J,2004,18(10):1120-1122.
[3]Kaiser A,Jenewein B,Pircher H,et al.Analysis of human papillomavirus E7 protein status in C-33A cervical cancer cells[J].Virus Genes,2015,50(1):12-21.
[4]Whitehead M,Ohlschlager P,Almajhdi FN,et al.Human papillomavirus(HPV)type 16 E7 protein bodies cause tumour regression in mice[J].BMC Cancer,2014,14:367.
[5]Jabbar SF,Park S,Schweizer J,et al.Cervical cancers require the continuous expression of the human papillomavirus type 16E7 oncoprotein even in the presence of the viral E6 oncoprotein[J].Cancer Res,2012,72(16):4008-4016.
[6]Pinto AP,Degen M,Villa LL,et al.Immunomarkers in gynecologic cytology:the search for the ideal'biomolecular Papanicolaou test'[J].Acta Cytol,2012,56(2):109-121.
[7]Jaiswal N,John R,Chand V,et al.Oncogenic human papillomavirus 16E7 modulates SUMOylation of Fox M1b[J].Int J Biochem Cell Biol,2015,58:28-36.
[8]Bodily JM,Mehta KP,Laimins LA.Human papillomavirus E7enhances hypoxia-inducible factor 1-mediated transcription by inhibiting binding of histone deacetylases[J].Cancer Res,2011,71(3):1187-1195.
[9]Woodman CB,Collins SI,Young LS.The natural history of cervical HPV infection:unresolved issues[J].Nat Rev Cancer,2007,7(1):11-22.
[10]宋丹,孔为民,张同庆,等.宫颈癌治疗后高危型人乳头瘤病毒转阴与预后关系研究[J].中国实用妇科与产科杂志,2017,33(9):975-978.