• 8/3/2006
  • Keith D. Hunter et al.
  • Cancer Research 66, 7405-7413, August 1, 2006

Most head and neck squamous cell carcinoma (HNSCC) patients present with late-stage cancers, which are difficult to treat. Therefore, early diagnosis of high-risk premalignant lesions and incipient cancers is important.

HNSCC is currently perceived as a single progression mechanism, resulting in immortal invasive cancers. However, we have found that 40% of primary oral SCCs are mortal in culture, and these have a better prognosis. About 60% of oral premalignancies (dysplasias) are also mortal. The mortal and immortal tumors are generated in vivo as judged by p53 mutations and loss of p16INK4A expression being found only in the original tumors from which the immortal cultures were derived.

To investigate the relationships of dysplasias to SCCs, we did microarray analysis of primary cultures of 4 normal oral mucosa biopsies, 19 dysplasias, and 16 SCCs. Spectral clustering using the singular value decomposition and other bioinformatic techniques showed that development of mortal and immortal SCCs involves distinct transcriptional changes. Both SCC classes share most of the transcriptional changes found in their respective dysplasias but have additional changes. Moreover, high-risk dysplasias that subsequently progress to SCCs more closely resemble SCCs than nonprogressing dysplasias.

This indicates for the first time that there are divergent mortal and immortal pathways for oral SCC development via intermediate dysplasias. We believe that this new information may lead to new ways of classifying HNSCC in relation to prognosis. (Cancer Res 2006; 66(15): 7405-13)

Authors:
Keith D. Hunter1,2, Johanna K. Thurlow1, Janis Fleming1, Paul J.H. Drake1, J. Keith Vass1, Gabriela Kalna3, Des J. Higham3, Pawel Herzyk4, D. Gordon MacDonald2, E. Ken Parkinson1 and Paul R. Harrison1

Authors’ affiliations:
1 The Beatson Institute for Cancer Research,
2 Oral Pathology, Glasgow Dental Hospital and School;
3 Department of Mathematics, University of Strathclyde; and
4 The Sir Henry Wellcome Functional Genomics Facility, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom