title: Dysregulation of CDK inhibitors and p53 in HPV-negative endocervical adenocarcinoma.
abstract: 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.
authors: 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.
authors: Makiko
authors: M
authors: Omori
authors: Akihiko
authors: A
authors: Hashi
authors: Tetsuo
authors: T
authors: Kondo
authors: Ryohei
authors: R
authors: Katoh
authors: Shuji
authors: S
authors: Hirata
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008875:Middle Aged; D015513:Oncogene Proteins / Q000378:metabolism; D030361:Papillomavirus Infections / Q000150:complications; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; C401561:CDK2AP2 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015513:Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27