Differential mechanisms of CDKN2A (p16) alteration in oral tongue squamous cell carcinomas and correlation with patient outcome. Issue 4 (30th January 2014)

• Record Type: Journal Article
• Authors: Lim, Annette M.; Do, Hongdo; Young, Richard J.; Wong, Stephen Q.; Angel, Christopher; Collins, Marnie; Takano, Elena A.; Corry, June; Wiesenfeld, David; Kleid, Stephen; Sigston, Elizabeth; Lyons, Bernard; Fox, Stephen B.; Rischin, Danny; Dobrovic, Alexander; Solomon, Benjamin
• Is Part Of: International journal of cancer. Volume 135:Issue 4(2014:Aug. 15)
• Page Start: 887
• Page End: 895
• Publication Date: 2014-01-30
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28727
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>CDKN2A (</italic>p16) disruption is reported as a frequent event in head and neck squamous cell carcinomas that confers poor prognosis. We investigated the frequency of different potential mechanisms of <italic>CDKN2A</italic> inactivation in oral tongue squamous cell carcinomas (OTSCC) and their impact on patient outcome. From a cohort of 153 OTSCC patients, 131 formalin fixed paraffin embedded blocks of pre‐treatment primary tumours were suitable for further molecular analysis. We assessed <italic>CDKN2A</italic> (p16) levels by immunohistochemistry (IHC), promoter methylation status by methylation‐sensitive high resolution melting, mutation status by Sanger sequencing, gene copy number variation by fluorescence in situ hybridisation, and correlated these with patient outcome. We found that the majority of OTSCC did not overexpress p16 (110/116, 95%), assessed by IHC. The frequency of <italic>CDKN2A</italic> mutations was 20% (21/103), homozygous loss was 7% (7/97), hemizygous loss 31% (30/97), and promoter methylation was 18% (20/113). We found no evidence of these mechanisms in 24/106 (23%) p16 IHC negative tumours. No significant correlation was identified between any potential mechanism of <italic>CDKN2A</italic> inactivation and clinical features, including smoking status and age. There was a non‐significant trend for worse overall survival for p16 IHC negative patients <italic>versus</italic> positive patients (HR = 1.81, 95% CI = 0.44–7.47, <italic>p =</italic> 0.40). No relationship was found between mechanisms of <italic>CDKN2A</italic> disruption and patient outcome. In conclusion, we demonstrate that <italic>CDKN2A</italic> alteration is a frequent event in OTSCC tumourigenesis. However, no correlation was identified between different potential mechanisms of <italic>CDKN2A</italic> disruption and clinical characteristics or patient outcome.</p> </abstract>