PATTERNS OF P53 AND KI-67 PROTEIN EXPRESSION IN EPITHELIAL DYSPLASIA FROM THE FLOOR OF THE MOUTH

Oral squamous cell carcinoma develops through a series of precancerous stages manifested at the microscopic level as epithelial dysplasia. M utation of the p53 tumour suppressor gene is thought to he an importan t component of oral carcinogenesis, p53 regulates cell proliferation a nd DNA repair by inhibiting the cell cycle at G1/S; loss of p53 functi on may therefore lead to aberrant cell kinetics, To date, no studies h ave examined the relationship between p53 protein and alterations in c ell kinetics in oral epithelial dysplasia from a single anatomical sit e, Serial sections were studied from 40 routinely processed biopsy spe cimens of epithelial dysplasia from the floor of the mouth, The expres sion of p53 protein was determined by immunohistochemistry and cell pr oliferation mas studied by immunostaining for the cell cycle-dependent protein Ki-67, The number of positive cells per millimetre of basemen t membrane was determined using computer image analysis and compared w ith site-matched normal controls, The mean p53 labelling index (LI) in normal mucosa vc sts low, 3.48 +/- 0.92 [mean +/- 95 per cent confide nce 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 mas 119.09 +/- 56.50, Difference s were also observed in the distribution of p53-positive cells between grades of dysplasia, with the development of compact p53-positive foc i 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 p 53 LI and Ki-67 score (r(2) = 0.37, P = 0.01). It is concluded that al tered p53 protein expression is probably an early event in oral carcin ogenesis in the floor of the mouth and is associated with dysregulatio n of cell proliferation at this site, (C) 1997 John Wiley & Sons, Ltd.