Cyclins play an important role in regulating the passage of dividing cells through critical checkpoints in cell cycle. Aberrant exprssion of cylcin proteins has been found in a number of human cancers, including carcinomas of the head and neck, where amplification of the cyclin D1 gene is a common finding. The obective of this study was to examine cell cycle kinetics in oral carcinomas by determining the expression the S phase protein cylcin A and the M phase protein cyclin B1. Routinely processed tissue sections of 50 oral squamous cell carcinomas from the floor of the mouth were stained by immunohistochemistry for cyclin A, cyclin B1 and Ki‐67 proteins. Ten specimens of normal epithelium from the floor of the mouth were used as controls. Teh number of cells showing nuclear staining for cylin A, cyclin B1 and Ki‐67 proteins was determined by computer image analysis. There were 17 well‐differentiated, 25 moderately differentiated and 8 poorly differentiated tumours. Mean counts for cylcin A (29.50 ± 4.10, Mean ± 95% CI), cyclin B1 (2.05 ± 0.30) and Ki‐67 (49.46 ± 5.91) protiens in the carcinomas were significantly higher than counts for the normal epithelial controls (cyclin A: 930 ± 1.72; cyclin B1: 1.01 ± 0.36; Ki‐67: 17.4. ± 4.17). For cyclin A, cyclin B1 and Ki‐67, mean staining scores fosr all tumour grades were significantly higher than controsl. There was a strong correlation between ki‐67 and cyclin A scores in all tumour groups (r2=0.68); however, the correlations between cyclin B1 and Cyclin A Scores(r2=0.35) and between clylcin B1 and ki‐67 scores (r2=0.39) were weak. We conclude that there is overexpression of cyclin A and cyclin B1 proteins in oral carcinoma. Furthermore, the poor correlations for cylcin B1 scores with other cell cycle indices suggest that there may be aberrant cell cycle progression at G2/M checkpoint in oral carcinomas.

Oral squamous cell carcinoma develops through a series of precancerous stages manifested at the microscopic level as epithelial dysplasia. Mutation of the p53 tumour suppressor gene is thought to be an important component of oral carcinogenesis. p53 regulates cell proliferation and DNA repair by inhibiting the cell cycle at G1/S; loss of p53 function may therefore lead to aberrant cell kinetics. To date, no studies have examined the relationship between p53 protein and alterations in cell kinetics in oral epithelial dysplasia from a single anatomical site. Serial sections were studied from 40 routinely processed biopsy specimens of epithelial dysplasia from the floor of the mouth. The expression of p53 protein was determined by immunohistochemistry and cell proliferation was studied by immunostaining for the cell cycle‐dependent protein Ki‐67. The number of positive cells per millimetre of basement membrane was determined using computer image analysis and compared with site‐matched normal controls. The mean p53 labelling index (LI) in normal mucosa was low, 3·48±0·92 [mean±95 per cent confidence interval (CI)], and increased sharply in the transition from mild (42·49±21·71) to moderate (104·86±51·39) epithelial dysplasia. The mean p53 LI for severe dysplasia was 119·09±56·50. Differences were also observed in the distribution of p53‐positive cells between grades of dysplasia, with the development of compact p53‐positive foci in severe dysplasia. Mean proliferative indices, as determined by Ki‐67 expression, were significantly associated with grade of epithelial dysplasia. Furthermore, there was a significant correlation between p53 LI and Ki‐67 score (r2=0·37, P=0·01). It is concluded that altered p53 protein expression is probably an early event in oral carcinogenesis in the floor of the mouth and is associated with dysregulation of cell proliferation at this site. © 1997 John Wiley & Sons, Ltd.

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Summary:Our aim was to examine the relationship between mouthrinse matrix metalloproteinases (MMPs) and whole albumin levels (AL) relative to oral mucositis (OM) in allogeneic stem cell transplant (alloSCT) patients. Mouthrinse vertebrate collagenase levels are positively correlated with connective tissue destruction (CTD) in periodontitis and may also be involved in CTD associated with OM. Increases in salivary AL have been noted prior to OM onset and may serve as a predictive tool for OM and as a positive control in this study. A total of 23 alloSCT patients were visited eight times over 4 weeks following the transplant. OM was scored via a previously validated examiner-based ordinal system. Mouthrinse samples were collected and analyzed for MMP-1, 8, 13 (members of the vertebrate collagenase group) and AL. No significant correlation was found for MMP levels relative to OM scores. AL were positively and significantly associated with OM scores (Po0.001). MMP levels may not be an important factor in OM development and severity; however, mouthrinse AL may serve as a more objective measure of OM development and severity.