Omori Makiko, Hashi Akihiko, Kondo Tetsuo, Katoh Ryohei, Hirata Shuji
Department of Obstetrics and Gynecology (M.O., A.H., S.H.) Department of Pathology (T.K., R.K.), Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Int J Gynecol Pathol. 2015 Mar;34(2):196-203. doi: 10.1097/PGP.0000000000000121.
Human papillomavirus (HPV)-negative adenocarcinoma (AC) is a minor subset of endocervical cancer, but its pathogenesis has yet to be elucidated. This study investigated the clinicopathologic features of HPV-negative endocervical AC (n=14) in comparison with HPV-positive endocervical AC (n=30), and further studied aberrations of cell-cycle regulators. Expression patterns of cyclin-dependent kinase inhibitors (p16, p14, p27, and p21) and p53 were evaluated immunohistochemically, and nuclear high-risk HPV DNA signals were detected by in situ hybridization and polymerase chain reaction. Immunoexpression of p16, p14, p27, p21, and p53 were observed in 90%, 67%, 77%, 40%, and 20% of HPV-positive ACs, and in 0%, 0%, 29%, 14%, and 57% of HPV-negative ACs, respectively. A higher frequency of lymph node metastasis and worse prognosis were significantly associated with HPV-negative AC. Our findings suggest that alteration of cyclin-dependent kinase inhibitors and p53 status may contribute to carcinogenesis and the clinical behavior of HPV-negative AC of the uterine cervix.
人乳头瘤病毒（HPV）阴性腺癌（AC）是宫颈内膜癌的一个较小的亚组，但其发病机制尚未阐明。本研究调查了HPV阴性宫颈内膜AC（n = 14）与HPV阳性宫颈内膜AC（n = 30）相比的临床病理特征，并进一步研究了细胞周期调节因子的异常。通过免疫组织化学评估细胞周期蛋白依赖性激酶抑制剂（p16、p14、p27和p21）和p53的表达模式，并通过原位杂交和聚合酶链反应检测核高危HPV DNA信号。p16、p14、p27、p21和p53的免疫表达分别在90%、67%、77%、40%和20%的HPV阳性AC中观察到，而在HPV阴性AC中分别为0%、0%、29%、14%和57%。淋巴结转移的较高频率和较差的预后与HPV阴性AC显著相关。我们的研究结果表明，细胞周期蛋白依赖性激酶抑制剂和p53状态的改变可能有助于子宫颈HPV阴性AC的致癌作用和临床行为。
