Expression of cyclin-dependent kinase 2-associated protein 1 confers an independent prognosticator in nasopharyngeal carcinoma: a cohort study

J Clin Pathol. 2012 Sep;65(9):795-801. doi: 10.1136/jclinpath-2012-200893. Epub 2012 Jul 12.

Abstract

Background and aim: Low expression of cyclin-dependent kinase 2-associated protein (CDK2AP1) is associated with tumour progression in oral and oesophageal carcinomas, but is not well studied in patients with head and neck cancer and nasopharyngeal carcinoma (NPC).

Methods: A rabbit anti-human CDK2AP1 polyclonal antibody was prepared. Immunoblotting of CDK2AP1 was examined in three cell lines and immunoexpression was retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines.

Results: Higher CDK2AP1 expression level was identified in dysplastic oral keratinocytes, compared with two NPC-derived HONE-1 and TW01 cell lines. Low expression of CDK2AP1 (50.8%) was correlated with advanced nodal status (p=0.002) and American Joint Committee on Cancer (AJCC) stage (p=0.004). In multivariate analyses, low CDK2AP1 expression emerged as an independent prognosticator for worse disease-specific survival (DSS; p=0.037) and local recurrence-free survival (LRFS; p=0.042), along with AJCC stage III-IV (p=0.034, DSS; p=0.029, LRFS).

Conclusions: Low CDK2AP1 expression is common and associated with adverse prognosticators, conferring tumour aggressiveness through cycle cycle, cell growth or apoptosis cellular processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Biopsy
  • Blotting, Western
  • Carcinoma
  • Cell Line, Tumor
  • Chi-Square Distribution
  • Disease Progression
  • Disease-Free Survival
  • Down-Regulation
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / mortality
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / therapy
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Transfection
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Biomarkers, Tumor
  • CDK2AP1 protein, human
  • Tumor Suppressor Proteins