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P16作为宫颈腺癌的分子生物标志物。

P16 as a molecular biomarker of cervical adenocarcinoma.

作者信息

Schorge John O, Lea Jayanthi S, Elias Keren J, Rajanbabu Ramababu, Coleman Robert L, Miller David S, Ashfaq Raheela

机构信息

Laboratory of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Tex, USA.

出版信息

Am J Obstet Gynecol. 2004 Mar;190(3):668-73. doi: 10.1016/j.ajog.2003.09.038.

DOI:10.1016/j.ajog.2003.09.038
PMID:15041997
Abstract

OBJECTIVE

Cervical adenocarcinomas are increasing in incidence each year. The aim of this study was to identify a molecular biomarker to improve early detection.

STUDY DESIGN

Fifty-five in situ and invasive cervical adenocarcinomas were compared with 5 normal endocervical controls by immunohistochemical analysis of p16, p21, p27, cyclin D1, cyclin E, p53, and Ki-67. Expression was scored from 0 to 8 by using an automated imaging system. Western blotting and polymerase chain reaction-based human papillomavirus (HPV) testing were performed on 16 of the invasive cases having fresh-frozen tissue.

RESULTS

P16 exhibited a higher mean expression score for in situ (7.4; P<.0001) and invasive cervical adenocarcinoma (6.6; P<.0001) versus controls (2.0). A cutoff p16 expression score of 5 had a sensitivity of 94.5% and a specificity of 100%. Western blotting confirmed p16 protein expression. Fourteen (88%) of 16 invasive cervical adenocarcinomas were HPV-positive.

CONCLUSION

P16 is a putative molecular biomarker of cervical adenocarcinoma. Overexpression appears to primarily reflect HPV-induced cell cycle dysregulation.

摘要

目的

宫颈腺癌的发病率逐年上升。本研究的目的是确定一种分子生物标志物以改善早期检测。

研究设计

通过对p16、p21、p27、细胞周期蛋白D1、细胞周期蛋白E、p53和Ki-67进行免疫组织化学分析,将55例原位和浸润性宫颈腺癌与5例正常宫颈内膜对照进行比较。使用自动成像系统将表达评分为0至8分。对16例有新鲜冷冻组织的浸润性病例进行了蛋白质印迹法和基于聚合酶链反应的人乳头瘤病毒(HPV)检测。

结果

与对照(2.0)相比,p16在原位宫颈腺癌(7.4;P<0.0001)和浸润性宫颈腺癌(6.6;P<0.0001)中表现出更高的平均表达评分。p16表达评分临界值为5时,敏感性为94.5%,特异性为100%。蛋白质印迹法证实了p16蛋白的表达。16例浸润性宫颈腺癌中有14例(88%)HPV呈阳性。

结论

p16是宫颈腺癌的一种假定分子生物标志物。过表达似乎主要反映HPV诱导的细胞周期失调。

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