Original Article

Virchows Archiv

, Volume 450, Issue 2, pp 161-167

First online:

Association of CDK4 and CCND1 mRNA overexpression in laryngeal squamous cell carcinomas occurs without CDK4 amplification

  • Alfons NadalAffiliated withAnatomia Patologica, Hospital Clínic, Institut d’Investigacions Biomediques “August Pi i Sunyer” (IDIBAPS)Departament de Biologia Cel·lular i Anatomia Patológica, Universitat de Barcelona Email author 
  • , Pedro JaresAffiliated withGenomics Unit, Institut d’Investigacions Biomediques “August Pi i Sunyer”(IDIBAPS), Universitat de Barcelona
  • , Magda PinyolAffiliated withGenomics Unit, Institut d’Investigacions Biomediques “August Pi i Sunyer”(IDIBAPS), Universitat de Barcelona
  • , Laura CondeAffiliated withFundació Clínic per a la Recerca Biomédica
  • , Coia RomeuAffiliated withHospital de Ntra. Sra. de Meritxell
  • , Pedro L. FernándezAffiliated withAnatomia Patologica, Hospital Clínic, Institut d’Investigacions Biomediques “August Pi i Sunyer” (IDIBAPS)Departament de Biologia Cel·lular i Anatomia Patológica, Universitat de Barcelona
  • , Elías CampoAffiliated withAnatomia Patologica, Hospital Clínic, Institut d’Investigacions Biomediques “August Pi i Sunyer” (IDIBAPS)Departament de Biologia Cel·lular i Anatomia Patológica, Universitat de Barcelona
  • , Antonio CardesaAffiliated withAnatomia Patologica, Hospital Clínic, Institut d’Investigacions Biomediques “August Pi i Sunyer” (IDIBAPS)Departament de Biologia Cel·lular i Anatomia Patológica, Universitat de Barcelona

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Abstract

CDK4 is involved in the control of G1–S phase transition as a part of the CCND1/CDK4 complexes. CCND1 and CDK4 gene alterations have been implicated in the development of different tumors. CCND1 has been associated with progression in laryngeal carcinomas. CDK4 protein overexpression was described associated to CCND1 overexpression in these tumors. However, the mechanisms implicated were not known. We analyzed CDK4 gene alterations and mRNA expression in a series of carcinomas of the larynx, and the results were compared to CCND1 expression and clinicopathological characteristics of the patients. CDK4 mRNA was overexpressed in 42 out of 60 tumors (70%) associated with CCND1 mRNA overexpression because 15 out of 16 cases with high CCND1 levels showed simultaneous increased levels of CDK4 mRNA (p = 0.023) and 12 (87%) of the tumors overexpressing both genes were in stage 4. No CDK4 gene amplifications, rearrangements, or mutations were detected in any of the tumors, including 24 overexpressed cases. These findings confirm that CDK4 overexpression is a frequent phenomenon in laryngeal carcinomas, which occurs at the transcriptional level but is related neither to gene amplification nor to gene mutation, and suggest that cooperation with CCND1 may be involved in the progression of laryngeal tumors.

Keywords

Larynx Head and Neck Oncogenes