Gupta Ruchi, Srinivasan Radhika, Nijhawan Raje, Suri Vanita, Uppal Radha
Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Indian J Pathol Microbiol. 2010 Jan-Mar;53(1):7-11. doi: 10.4103/0377-4929.59174.
The association of human papilloma virus (HPV) infection and cervical intraepithelial neoplasia (CIN) is well recognized. Interaction of HPV oncogenic proteins with cellular regulatory proteins leads to up regulation of p16 INK4A , a CDK inhibitor, which is a biomarker for HPV infection. We investigated p16 expression in CIN and invasive squamous cell carcinoma (SCC) which has not been reported in the Indian population previously.
Retrospective analysis of 100 cases with 20 cases each of histologically normal cervical epithelium, CIN1, 2, 3 and invasive SCC for p16 expression was performed by immunohistochemistry using commercially available mouse monoclonal antibody to p16 (clone 6H12).
For differences in expression among groups, statistical analysis was carried out using ANOVA and post hoc test of Scheffe.
p16 immunoreactivity was found to be both nuclear and/or cytoplasmic. The normal cervical epithelium was predominantly negative for p16 (18/20). There was a progressive increase of p16 expression with the grade of CIN. In CIN 1, two cases (20%) showed nuclear and nucleocytoplasmic positivity respectively. In contrast, diffuse strong nuclear or nucleocytoplasmic expression was observed in 45 and 55% cases of CIN 2 and CIN 3 respectively. All except one squamous cell carcinoma stained strongly positive for p16. The difference in expression between CIN 2/3 and SCC versus normal cervix was found highly significant (p is equal to 0.008 and p less than 0.001).
p16 expression correlates excellently with the grade of CIN and is a sensitive marker of cervical intraepithelial neoplasia.
人乳头瘤病毒（HPV）感染与宫颈上皮内瘤变（CIN）之间的关联已得到充分认可。HPV致癌蛋白与细胞调节蛋白的相互作用导致细胞周期蛋白依赖性激酶抑制剂p16INK4A上调，p16INK4A是HPV感染的生物标志物。我们调查了CIN和浸润性鳞状细胞癌（SCC）中p16的表达情况，此前印度人群中尚未有相关报道。
回顾性分析100例病例，其中组织学正常的宫颈上皮、CIN1、2、3和浸润性SCC各20例，使用市售的抗p16小鼠单克隆抗体（克隆6H12）通过免疫组织化学检测p16的表达。
对于各组间表达差异，采用方差分析和谢费事后检验进行统计分析。
发现p16免疫反应性存在于细胞核和/或细胞质中。正常宫颈上皮p16主要为阴性（18/20）。随着CIN分级增加，p16表达逐渐升高。在CIN 1中，分别有2例（20%）显示细胞核和核质阳性。相比之下，CIN 2和CIN 中分别有45%和55%的病例观察到弥漫性强细胞核或核质表达。除1例鳞状细胞癌外，所有病例p16染色均为强阳性。发现CIN 2/3和SCC与正常宫颈之间的表达差异具有高度显著性（p = 0.008，p < 0.001）。
p16表达与CIN分级密切相关，是宫颈上皮内瘤变的敏感标志物。
