Histopathological and immunohistochemical study of malignant transformation of oral leukoplakia, with special reference to apoptosis-related gene products and proliferative activity

Abstract

Objective—To examine the frequency of apoptosis in oral leukoplakia and its relationship with pathological parameters, including Ki-67 expression, and with the expression of p53, Bcl-2 and Bax proteins. Material and Methods—Clinical, histopathological and immunohistochemical studies were carried out and the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling method was used to verify the apoptosis and its mechanism of genetic control of the development, progression and promotion of lesions. The material consisted of five normal mucosal epithelia. six leukoplakias without malignant transformation and seven leukoplakias with malignant transformation. Based on counts of 10 fields at a magnification of x 400, mitotic, apoptotic and Ki-67 indices were calculated, and p53, Bcl-2 and Bax expressions were recorded. Results—The peak of the mitotic and Ki-67 indices and p53 expression shifted basally, possibly as a result of malignant transformation, whilst the peak of apoptosis and the expression of apoptotic-related proteins in oral leukoplakia showed no transformation. Conclusions—The frequent expression of Bcl-2 in oral leukoplakia with malignant transformation combined with the reduction in the number of apoptotic cells indicated that malignancy occurred as a result of the avoidance of apoptosis. In addition, high levels of Bax expression in oral leukoplakia without malignant transformation indicated that the Bcl family may play a role in the progression of the disease.

• Bax
• Bcl-2
• Ki-67
• oral pathology
• p53
• precancerous lesions
• terminaldeoxynucleotide transferase-mediated dUTP nick-end labeling