Changes in Apoptosis and Mitotic Index, p53 and Ki67 Expression in Various Types of Oral Leukoplakia

Abstract

Introduction: Leukoplakia is the most frequent pre-blastomatous alteration in the oral cavity. Its potential for malignant transformation is unpredictable. The aim of the present study was to provide data about the processes and molecular genetic background of this disease. Materials and Methods: Leukoplakias of 15 patients and oral squamous cell carcinomas of 3 patients treated at the Department of Periodontology and Oral Surgery, Semmelweis University, were studied by histological and immunohistochemical methods. The samples were fixed in 4% formalin and embedded in paraffin. Hematoxylin and eosin staining, TUNEL reaction (Apop-Detect kit), and immunohistochemical reactions for Ki67 and p53 were applied. The severity of dysplasia, the mitotic and apoptotic indices and expression as well as distribution of Ki67 and p53 were examined and compared to the clinical appearance of leukoplakia. Results: The mitotic and apoptotic indices and Ki67 expression increased significantly in parallel with the severity of dysplasia and also with the clinical stage (homogenous, nodular, erythroleukoplakia). The positivity and intracellular localization of (mutant) p53 varied according to the clinical form of leukoplakia. Homogenous and nodular forms showed cytoplasmic staining, while erythroleukoplakia and carcinoma cases were characterized by nuclear positivity. Conclusions: The increased apoptotic and Ki67 indices may indicate an unfavorable prognosis for leukoplakia. The expression of Ki67 and p53 in various forms of leukoplakia point to the increasing instability of the genome in parallel with the severity of leukoplakia.