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Cyclin D1 amplification is independent of p16 inactivation in head and neck squamous cell carcinoma

Oncogene volume 18, pages 3541–3545 (1999)Cite this article

Abstract

Progression through the G1 phase of the cell cycle is mediated by phosphorylation of the retinoblastoma protein (pRb) resulting in the release of essential transcription factors such as E2F-1. The phosphorylation of pRb is regulated positively by cyclin D1/CDK4 and negatively by CDK inhibitors, such as p16 (CDKN2/MTS-1/INK4A). The p16 /cyclin D1/Rb pathway plays a critical role in tumorigenesis and many tumor types display a high frequency of inactivation of at least one component of this pathway. In order to determine the overall contribution of these three components to progression of head and neck squamous cell carcinoma (HNSCC), we examined p16 inactivation, cyclin D1 amplification, and pRb expression in 23 primary HNSCC tumors and five cell lines. p16 inactivation was detected in 19/23 (83%) primary tumors by detailed genetic analysis and was confirmed by immunohistochemistry (IHC). Absence of Rb protein expression indicative of pRb inactivation was identified in 2/23 (9%) tumors. In this set of tumors, there was a perfect inverse correlation between p16 and pRb inactivation. Using fluorescence in situ hybridization (FISH) cyclin D1 amplification was identified in 4/5 (80%) cell lines and 4/11 (36%) primary tumors. However, 2/4 cell lines and all four primary tumors with cyclin D1 amplification contained a concomitant alteration of p16. Therefore 21/23 (91%) of primary HNSCC contained at least one alteration in the p16/cyclin D1/Rb pathway. Although p16 and Rb alteration are apparently exclusive, cyclin D1 amplification occurs concomitantly with the loss of p16 suggesting an additional role for this amplification in HNSCC.

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Abbreviations

pRb:

retinoblastoma protein

cdk:

cyclin dependent kinase

p16 :

CDKN2/MTS-1/INK4A

HNSCC:

Head and Neck Squamous Cell Carcinoma

IHC:

immunohistochemistry

FISH:

fluorescence in situ hybridization

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Authors and Affiliations

  1. Department of Otolaryngology Head & Neck Surgery, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, 818 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205-2196, Maryland, USA

    K Okami, A L Reed, P Cairns, W M Koch, S Wehage, J Jen & D Sidransky

  2. Department of Pathology, 7181 Meyer Building, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287, Maryland, USA

    W H Westra

  3. Department of Otolaryngology, Yamaguchi University, Ube, 755, Japan

    K Okami

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  1. K Okami
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  2. A L Reed
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  4. W M Koch
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  7. J Jen
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  8. D Sidransky
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Okami, K., Reed, A., Cairns, P. et al. Cyclin D1 amplification is independent of p16 inactivation in head and neck squamous cell carcinoma. Oncogene 18, 3541–3545 (1999). https://doi.org/10.1038/sj.onc.1202837

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