title: Divergent routes to oral cancer.
abstract: 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 approximately 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 p16(INK4A) 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.
authors.affiliation: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, UK.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Hunter
authors.forename: Johanna K
authors.initials: JK
authors.lastname: Thurlow
authors.forename: Janis
authors.initials: J
authors.lastname: Fleming
authors.forename: Paul J H
authors.initials: PJ
authors.lastname: Drake
authors.forename: J Keith
authors.initials: JK
authors.lastname: Vass
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kalna
authors.forename: Des J
authors.initials: DJ
authors.lastname: Higham
authors.forename: Pawel
authors.initials: P
authors.lastname: Herzyk
authors.forename: D Gordon
authors.initials: DG
authors.lastname: Macdonald
authors.forename: E Ken
authors.initials: EK
authors.lastname: Parkinson
authors.forename: Paul R
authors.initials: PR
authors.lastname: Harrison
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53