Apoptosis-associated proteins and the development of oral squamous cell carcinoma

Expression of apoptosis-associated proteins was evaluated in premalignant a nd malignant oral epithelial lesions, to test the hypothesis that protein r egulation of apoptosis may be altered in the development of oral squamous c ell carcinoma. Ninety archived paraffin-embedded specimens from 25 patients (two or more sequential biopsies each) and eight control specimens were ev aluated in immunohistochemically stained sections for tumor suppressor prot ein p53, p53 binding protein mdm-2, and apoptosis regulatory proteins Bcl-2 , Bcl-X, Bax, and Bak. The initial histologic diagnosis for 17/25 patients was either focal keratosis, mild dysplasia, or moderate dysplasia; the init ial diagnosis for the remaining eight patients ranged from severe dysplasia to moderately differentiated squamous cell carcinoma. Thirty of 90 specime ns showed positive p53 expression, nine of which were dysplasias. In patien ts with one or more lesions displaying p53 expression, there was increased intensity of staining with disease progression. Bak was expressed in 57/90 specimens, including 27 dysplasias of various grades. There was also a sign ificantly increased intensity of Bak staining with disease progression, whi ch did not appear to be dependent upon p53 status. Bcl-X was expressed in 7 3/90 specimens, with staining displayed earlier in premalignant lesions tha n either p53 or Bak. Ten of 90 specimens were positive for Bcl-2 tall were dysplasias or carcinomas), and only 2/90 specimens were positive for Bax. E leven of 90 specimens were positive for mdm-2; six of which were also posit ive for p53. These data show that apoptosis-associated proteins are altered in variable patterns in both premalignant and malignant oral epithelial le sions, p53 and especially Bak and Bcl-X are expressed early; Bax is largely absent; and Bcl-2 and mdm-2 show sporadic expression in the development of oral premalignant and malignant disease. (C) 1998 Elsevier Science Ltd. Al l rights reserved.