Cell cycle proteins and the development of oral squamous cell carcinoma

Expression of cell cycle regulatory proteins was evaluated in premalignant and malignant oral epithelial lesions, to test the hypothesis that protein regulation of the cell cycle may be altered in the development of oral squa mous cell carcinoma. Archived paraffin-embedded specimens (n = 90) from 25 patients with recurrent or persistent lesions were evaluated in immunohisto chemically stained sections for cell cycle regulatory proteins p53, Rb, Cyc lin D1, p27, and p21. The cell cycle was also evaluated by expression of nu clear protein Ki 67. Sections were graded semiquantitatively using a 0 - 3 + scale to indicate the percentage of positively stained cells. The initial histologic diagnosis for 17/25 patients was either focal keratosis, mild d ysplasia, or moderate dysplasia; the initial diagnosis for the remaining ei ght patients ranged from severe dysplasia to moderately differentiated squa mous cell carcinoma. Thirty-three of 90 specimens showed positive p53 expre ssion, 11 of which were dysplasias, Eighty-nine of 90 specimens, from all s tages of disease, showed positive Rb expression. Twenty-three of 90 specime ns: showed positive Cyclin D1 expression, typically in the later stages (ca rcinoma) of a patient's disease. Eighty-four of 90 specimens showed positiv e p21 expression; while 55 of 90 specimens were positive for p27. In contro l mucosa, p27 was highly expressed, while Rb and p21 proteins were expresse d at relatively low levels; p53 and Cyclin D1 proteins were largely absent. Generally, staining of p53, Rb, p21, and Ki 67 increased with time in seri al biopsies, while p27 showed decreased staining with disease progression. These data show that cell cycle regulatory proteins are altered in both pre malignant and malignant disease, and that protein phenotypes are heterogene ous. P53 expression is seen early, and Cyclin D1 expression is seen late in the development of oral premalignant and malignant disease. Expression of p53, Rb, p21 and Ki67 increased, while p27 decreased, with disease progress ion. (C) 1999 Elsevier Science Ltd. All rights reserved.