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CpG island methylation phenotype (CIMP) in oral squamous cell carcinoma: associated with a marked inflammatory response and less aggressive tumour biology

Shaw, Richard J.; Hall, Gillian L.; Lowe, Derek; Bowers, Naomi L.; Liloglou, Triantafillos; Field, John K.; Woolgar, Julia A. and Risk, Janet M. (2007) CpG island methylation phenotype (CIMP) in oral squamous cell carcinoma: associated with a marked inflammatory response and less aggressive tumour biology. Oral Oncology, 43 (9). pp. 878-886. ISSN 1368-8375

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Abstract

Studies in several tumour sites highlight the significance of the CpG island methylation phenotype (CIMP), with distinct features of histology, biological aggression and outcome. We utilise pyrosequencing techniques of quantitative methylation analysis to investigate the presence of CIMP in oral squamous cell carcinoma (OSCC) for the first time, and evaluate its correlation with allelic imbalance, pathology and clinical behaviour. Tumour tissue, control tissue and PBLs were obtained from 74 patients with oral squamous cell carcinoma. Pyrosequencing was used to analyse methylation patterns in 75–200 bp regions of the CpG rich gene promoters of 10 genes with a broad range of cellular functions. Allelic imbalance was investigated using a multiplexed panel of 11 microsatellite markers. Corresponding variables, histopathological staging and grading were correlated with these genetic and epigenetic aberrations. A cluster of tumours with a greater degree of promoter methylation than would be predicted by chance alone (P = 0.001) were designated CIMP+ve. This group had less aggressive tumour biology in terms of tumour thickness (p = 0.015) and nodal metastasis (P = 0.012), this being apparently independent of tumour diameter. Further, it seems that these CIMP+ve tumours excited a greater host inflammatory response (P = 0.019). The exact mechanisms underlying CIMP remain obscure but the association with a greater inflammatory host response supports existing theories relating these features in other tumour sites. As CIMP has significant associations with other well documented prognostic indicators, it may prove beneficial to include methylation analyses in molecular risk modelling of tumours.

Item Type:Article
Additional Information:Issue: October 2007. Available online 25 January 2007.
Uncontrolled Keywords:CIMP; oral squamous cell carcinoma; methylation; allelic imbalance
Subjects:R Medicine > RK Dentistry
Departments, Research Centres and Related Units:Academic Faculties, Institutes and Research Centres > Faculty of Medicine > School of Dental Sciences
DOI:10.1016/j.oraloncology.2006.10.006
Refereed:Yes
Status:Published
ID Code:1108
Deposited On:30 Mar 2009 10:17
Last Modified:21 Mar 2012 11:59

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