Dysregulation of CDK inhibitors and p53 in HPV-negative endocervical adenocarcinoma

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.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / virology
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Middle Aged
  • Oncogene Proteins / metabolism
  • Papillomavirus Infections / complications
  • Polymerase Chain Reaction
  • Tumor Suppressor Protein p53 / metabolism
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / virology


  • Biomarkers, Tumor
  • CDK2AP2 protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Oncogene Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Cyclin-Dependent Kinase Inhibitor p27