Ishikawa Mitsuya, Fujii Takuma, Masumoto Nobuo, Saito Miyuki, Mukai Makio, Nindl Ingo, Ridder Ruediger, Fukuchi Takeshi, Kubushiro Kaneyuki, Tsukazaki Katsumi, Nozawa Shiro
Department of Obstetrics, Keio University School of Medicine, Tokyo, Japan.
Int J Gynecol Pathol. 2003 Oct;22(4):378-85. doi: 10.1097/01.pgp.0000092135.88121.1f.
As human papillomavirus (HPV) infection is the main risk factor for squamous cell carcinoma of the cervix and overexpression of p16INK4a occurs when retinoblastoma protein is inactivated by high-risk HPV, the authors studied the association of HPV infection and expression of p16INK4a in cervical adenocarcinomas. Specimens of cervical glandular neoplasias were immunostained with a p16INK4a-specific monoclonal antibody (clone E6H4). Approximately 80% of glandular neoplasms showed overexpression of p16INK4a. Exfoliated cells from 14 adenocarcinomas were further examined by p16INK4a-specific immunocytochemistry, and 12 cases showed overexpression of p16INK4a, suggesting that immunostaining for p16INK4a may be a useful diagnostic tool for cervical adenocarcinomas. The authors further examined HPV DNA in cervical adenocarcinomas with the polymerase chain reaction method. Overexpression of p16INK4a was positive in 94% of cases in which HPV16 or 18DNA was positive, a finding suggesting that HPV16 or 18 may play an important role in cervical adenocarcinomas. Overexpression of p16INK4a may be an indicator of pathogenic activity of high-risk HPVs.
由于人乳头瘤病毒（HPV）感染是宫颈鳞状细胞癌的主要危险因素，且当视网膜母细胞瘤蛋白被高危型HPV灭活时会出现p16INK4a的过表达，因此作者研究了HPV感染与宫颈腺癌中p16INK4a表达之间的关联。用p16INK4a特异性单克隆抗体（克隆E6H4）对宫颈腺性肿瘤标本进行免疫染色。约80%的腺性肿瘤显示p16INK4a过表达。对14例腺癌的脱落细胞进一步采用p16INK4a特异性免疫细胞化学检测，12例显示p16INK4a过表达，提示p16INK4a免疫染色可能是宫颈腺癌有用的诊断工具。作者进一步采用聚合酶链反应法检测宫颈腺癌中的HPV DNA。在HPV16或18 DNA阳性的病例中，94%的病例p16INK4a过表达呈阳性，这一结果提示HPV16或18可能在宫颈腺癌中起重要作用。p16INK4a过表达可能是高危型HPV致病活性的一个指标。
