CCND1 amplification and cyclin D1 immunohistochemical expression in head and neck squamous cell carcinomas

Clin Oral Investig. 2014 Jan;18(1):269-76. doi: 10.1007/s00784-013-0967-6. Epub 2013 Mar 15.

Abstract

Objectives: Gene products, which show a significant association to cell proliferation and cell cycle control, are of high scientific interest, because genes as well as gene products could be possible targets for a specific therapeutic approach and eventually be prognostic markers.

Materials and methods: Cyclin D1 expression and amplification as well as the Ki-67 expression status were examined in a two tissue microarray analysis for head and neck squamous cell carcinoma (HNSCC) including 546 patients. A tumour site-specific analysis and a survival analysis of 222 oral squamous cell carcinoma (OSCC) patients were performed. Cyclin D1 amplification status was examined with fluorescence in situ hybridisation analysis, while cyclin D1 expression and Ki-67 expression status were examined with IHC.

Results: Amplification of the CCND1 gene and immunohistochemical expression of cyclin D1 and Ki-67 were examined in 546 tumours of the head and neck region in two tissue microarrays. CCND1 amplification was significantly more frequent in pharyngeal carcinomas (63%) than in laryngeal (37%) and oral (25%) carcinomas. Among the 222 cases of OSCCs, both CCND1 amplification and cyclin D1 expression were significantly associated with overall survival of the patients (p = 0.0127 and p = 0.0004, respectively). Ki-67 expression was significantly associated with cyclin D1 expression and with amplification of the CCND1 gene (p = 0.0002 and p = 0.0015, respectively) but not with patient overall survival.

Conclusion: Our results suggest the prognostic value of CCND1 amplification and cyclin D1 expression for patients with OSCC and highlight the genetic differences in HNSCC of different subanatomic localisation.

Clinical relevance: Cyclin D1 expression and CCND1 amplification seem to have a prognostic value for OSCC. Further studies of HNSCC should always consider subanatomic genetic differences.

MeSH terms

  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Ki-67 Antigen / metabolism
  • Lymphatic Metastasis
  • Survival Analysis

Substances

  • CCND1 protein, human
  • Ki-67 Antigen
  • Cyclin D1