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中华妇幼临床医学杂志(电子版) ›› 2009, Vol. 05 ›› Issue (06) : 572 -576. doi: 10.3877/cma.j.issn.1673-5250.2009.06.102

论著

宫颈病变组织中p16蛋白表达及其与人乳头瘤病毒感染的关系
陈伟芳, 张江宇, 李荔, 罗喜平   
  1. 510010 广州,广州医学院附属广东省妇儿医院妇科
    510010 广州,广州医学院附属广东省妇儿医院病理科
  • 出版日期:2009-12-01

P16 Expression and Its Correlation With Human Papillomavirus Infection in Cervical Lesions

Wei-fang CHEN, Jiang-yu ZHANG, Li LI, Xi-ping LUO   

  1. Department of Obstetrics and Gynecology, Guangzhou Medical College Affiliated Guangdong Province Women and Children Hospital, Guangzhou 510010, China
  • Published:2009-12-01
  • Supported by:
    *Project No. 5000166A, supported by the Natural Science Foundation of Guangdong Province
引用本文:

陈伟芳, 张江宇, 李荔, 罗喜平. 宫颈病变组织中p16蛋白表达及其与人乳头瘤病毒感染的关系[J]. 中华妇幼临床医学杂志(电子版), 2009, 05(06): 572-576.

Wei-fang CHEN, Jiang-yu ZHANG, Li LI, Xi-ping LUO. P16 Expression and Its Correlation With Human Papillomavirus Infection in Cervical Lesions[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2009, 05(06): 572-576.

目的

探讨宫颈癌(cervical cancer)及其癌前病变组织中p16蛋白表达及其与人乳头瘤病毒(human papillomavirus,HPV)感染的关系。

方法

采用免疫组化(immunohistochemistry,IHC)SP法检测40例宫颈浸润癌(invasive carcinoma of cervix,ICC)标本(ICC组)、20例低度宫颈上皮内瘤样病变(cervical intraepithelial neoplasia Ⅰ,CIN Ⅰ)标本(CIN Ⅰ组)、30例高度宫颈上皮内瘤样病变(CIN Ⅱ~Ⅲ)(CIN Ⅱ~Ⅲ组)标本和20例正常宫颈组织标本(对照组)的p16蛋白表达;用导流杂交基因芯片技术(HybriMax)测定上述标本的人乳头瘤病毒分型。

结果

P16蛋白在正常宫颈上皮(对照组)无表达,在宫颈癌及癌前病变组织呈现过表达(ICC组,CIN Ⅰ组,CIN Ⅱ~Ⅲ组);在CIN Ⅰ,CINI Ⅰ~Ⅲ,ICC组过表达率分别为35.0%,83.3%和100.0%。P16蛋白表达随宫颈病变级别进展而增加(P<0.001)。高危人乳头状瘤病毒在正常宫颈上皮(对照组)的感染率为0,CINⅠ,CINⅡ~Ⅲ,ICC组分别为55.0%,80.0%和92.5%。HPV–16和(或)–18亚型是宫颈癌及癌前病变最常见感染亚型。P16蛋白过表达在高危型人乳头瘤病毒(high–risk human papillomavirus,HR–HPV)感染宫颈组织明显高于HPV呈阴性或低危型人乳头瘤病毒(low–risk human papillomavirus,LR–HPV)感染宫颈组织(P<0.05)。

结论

P16蛋白过表达,可用于区分正常宫颈和宫颈癌前病变及宫颈浸润癌组织。P16蛋白过表达与高危型人乳头瘤病毒感染有关。

Objective

To evaluate the expression and correlation among p16 protein, infection of human papillomavirus (HPV) in invasive cervix carcinoma (ICC) and cervical intraepithelial neoplasia (CIN).

Methods

The immunohistochemical staining SP method was used to detect the expression of p16 protein and HybriMax was used to examine types of human papillomavirus in 40 cases of invasive carcinoma of cervix(ICC group), 20 cases of CIN Ⅰ (CIN Ⅰ group), 30 cases of CINⅡ~Ⅲ (CINⅡ~Ⅲ group), and 20 cases of normal cervix tissues(control group).

Results

①There was no positive expression of p16 protein in normal cervix tissues (control group), but the over expression rates of CIN Ⅰ group, CIN Ⅱ~Ⅲ group, and ICC group were 35.0%, 83.3%, and 100.0%, respectively. There was a significant trend of increasing expression from normal cervix or CINⅠ to invasive carcinoma of cervix (P<0.05). ② The infection of high-risk human papillomavirus (HR-HPV) had been detected as negative in normal cervical samples, but 55.0% in CIN Ⅰ group, 80.0% in CIN Ⅱ~Ⅲ group, 92.5% in ICC group. HPV-16/-18 were predominant types(50%) of high-risk human papillomavirus infection in cervical intraepithelial neoplasia and invasive carcinoma of cervix tissue samples. ③There were significant positive correlations between the expression of p16 protein and high-risk human papillomavirus in cervical intraepithelial neoplasia and invasive carcinoma of cervix tissue samples(P<0.05).

Conclusion

Cervical intraepithelial neoplasia expresses p16 protein which has malignant proneness. The investigation of p16 protein may used as a supplementary test for screening and routine diagnosis of cervical lesions. The over expressions of p16 protein may related with high-risk human papillomavirus infection.

图1 p16在宫颈CINⅡ组织中的阳性表达,病变细胞质及细胞核联合染色(SP×400)
图2 p16在宫颈鳞状细胞癌组织中的阳性表达,病变细胞质及细胞核联合染色(SP×400)
1 International Agency for Research on Cancer. Cervical cancer screening. IARC handbooks of cancer prevention, vol 10. Lyon: IARC/WHO, 2005, 302.
2 Tsai CH, Yang CC, Chou LS, et al. The correlation between alteration of p16 gene and clinical status in oral squamous cell carcinoma. J Oral Pathol Med, 2001, 30(9):527–531.
3 Ueki T, Hsing AW, Gao YT, et al. Alterations of p16 and prognosis in biliary tract cancers from a population–based study in China. Clin Cancer Res, 2004, 10(5): 1717–1725.
4 Xin H, Geng M, Chen SF, et al. Evaluation of expressions and clinical significance of p16~(INK4a) and PCNA in uterine cervix carcinoma and cervical intraepithelial neoplasia. Chin J Cancer Prev Treat, 2007, 10(20): 1563–1567.[辛海,耿明,陈诵芬,等.宫颈癌及其癌前病变组织中p16INK4a和PCNA的表达及临床意义.中华肿瘤防治杂志,2007, 10(20): 1563–1567.]
5 Liu P, Liu YL. Prospective cohort research on cervical carcinoma screening of thinprep cytological test combined with human papilloma virus hybrid capture. Chin J Obstet Gynecol Pediatr (Electron Ed), 2009, 5(1): 18–22.[刘萍,刘岩丽.液基薄层宫颈刷片细胞学检查结合二代杂交捕获法人乳头瘤病毒筛查宫颈癌的前瞻性队列研究(J/CD). 中华妇幼临床医学杂志:电子版,2009, 5(1): 18–22.]
6 Klaes R, Benner A, Friedrich T, et al. p16 INK4a immunohistochemistry improves interobserver agreement in the diagnosis of cervical intraepithelial neoplasia. Am J Surg Pathol, 2002, 26(11): 1389–1399.
7 Keating JT, Cviko A, Riethdorf S, et al. Ki–67, cyclin E, and p16INK4 are complimentary surrogate biomarkers for human papilloma virus–related cervical neoplasia. Am J Surg Pathol, 2001, 25(7): 884–891.
8 Murphy N, Ring M, Killalea AG, et al. p16INK4A as a marker for cervical dyskaryosis: CIN and cGIN in cervical biopsies and ThinPrep smears. J Clin Pathol, 2003, 56(1): 56–63.
9 Fregonesi PA, Teresa DB, Duarte RA, et al. p16(INK4A) immunohistochemical overexpression in premalignant and malignant oral lesions infected with human papillomavirus. J Histochem Cytochem, 2003, 51(10): 1291–1297.
10 Lang JC, Borchers J, Danahey D, et al. Mutational status of overexpressed p16 in head and neck cancer: Evidence for germLine mutation of p16/p14ARF. Int J Oncol, 2002, 21(2): 401–408.
11 Lin ZH, Shen XH, Jin Z, et al. Human papillomavirus genotyping by oligonucleotide microarray and p16 expression in uterine cervical intraepithelial neoplasm and in invasive carcinoma in Korean women. Pathol Int, 2005, 55(8): 491–496.
12 Matsukura T, Sugase M. Identification of genital human papillomaviruses in cervical biopsy specimens: Segregation of specific virus types in specific clinicopathologic lesions. Int J Cancer, 1995, 61(1): 13–22.
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