title: A minimally invasive immunocytochemical approach to early detection of oral squamous cell carcinoma and dysplasia.
abstract: Squamous dysplasia of the oral cavity indicates increased risk of progression to squamous cell carcinoma (SCC). An important advance would be the development of a minimally invasive assay for identification of oral SCC and dysplasia. We have investigated the suitability in this context of immunostaining oral smears for minichromosome maintainance proteins (MCMs), sensitive and specific biomarkers of cell cycle entry. Immunohistochemical examination of 66 oral tissue samples showed a greater frequency of Mcm-2 expression in surface layers of moderate/severe dysplasia and SCC compared to benign keratosis/mild dysplasia. Immunocytochemistry for Mcm-2/Mcm-5 was performed on 101 oral smears. Conventional smears included 23 from normal mucosa, benign proliferative disease and mild dysplasia, all of which were MCM negative. Of 52 conventional smears of SCC tissue samples, 18 were inadequate. However, MCM-positive cells were present in 33/34 adequate samples. Of 26 liquid-based cytology smears, 19 out of 20 smears from SCC were adequate and all were MCM positive. Six smears from benign lesions were adequate and MCM negative. We conclude that MCMs are promising markers for early detection of oral SCC and dysplasia, particularly in a liquid-based cytology platform. Detection of MCMs would be amenable to automation and potentially applicable in the developing world. Further studies are now warranted.
authors.affiliation: MRC Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, and Department of Oral Pathology, King's College London Dental Institute, Guy's Hospital, London, UK.
authors.forename: I S
authors.initials: IS
authors.lastname: Scott
authors.forename: E
authors.initials: E
authors.lastname: Odell
authors.forename: P
authors.initials: P
authors.lastname: Chatrath
authors.forename: L S
authors.initials: LS
authors.lastname: Morris
authors.forename: R J
authors.initials: RJ
authors.lastname: Davies
authors.forename: S L
authors.initials: SL
authors.lastname: Vowler
authors.forename: R A
authors.initials: RA
authors.lastname: Laskey
authors.forename: N
authors.initials: N
authors.lastname: Coleman
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000032:analysis* / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D064111:Minichromosome Maintenance Complex Component 2; D009061:Mouth Mucosa / Q000737:chemistry / Q000473:pathology; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis* / Q000096:biosynthesis; D016612:Paraffin Embedding; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000473:pathology; D012680:Sensitivity and Specificity; D013194:Staining and Labeling; D020858:Tissue and Organ Harvesting / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2