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.

Inhibition of DMBA‐induced Oral Squamous Cells Carcinoma Growth by Brazilian Red Propolis in Rodent Model

“…As elevation of p21 after PLK-1 inhibition has been regarded as a general phenomenon in normal and cancer cells [43], the retarded growth of HERP-treated tumours may also be associated with the inhibitory effects of biochanin A on tumour cell proliferation. In oral mucosal lesions, the expression of Ki-67 increases according to the proliferative activity and degree of epithelial dysplasia, suggesting that it is a marker of the progression from epithelial dysplasia to carcinoma [25,44]. In the present study, no significant difference in the immunohistochemical expression of Ki-67 was observed among the cases of OSCC irrespective of the oral administration of HERP.…”

p53 Expression Helps Identify High Risk Oral Tongue Premalignant Lesions and Correlates with Patterns of Invasive Tumour Front and Tumour Depth in Oral Tongue Squamous Cell Carcinoma Cases

“…Our observation that p53 expression increases with severity of dysplasia has been reported in earlier studies as well. (Girod et al, 1998;Iwasa et al, 2001;Kovesi et al, 2003;2012). None of the tongue dysplasia showed p53 nuclear positive expression in >50% of cells unlike tumours where we had p53 overexpression identified in 76.1% of the positive tumours.…”

Transformation analysis of oral epithelial dysplasia to carcinoma in-situ and squamous cell carcinoma by p53 expression and gene mutations

“…12 Many studies reported that the p53 protein overexpression is frequently found in both malignant and dysplastic lesions which increased due to grades of dysplasia, and may be an early event in multistage carcinogenesis of head and neck cancer. [13][14][15][16][17]18 The abnormal p53 protein expression reported in 10 to 80% of oral SED [19][20][21][22]24 that some cases related to p53 gene mutation, 13,14,24,25 and nearly 60% of human cancers are accompanied by mutation in p53 gene, 13 however, in some cases it is possible to observe protein over expression but they did not show any mutation gene or p53 gene mutation. 25 As reported before, oral CIS have shown p53 gene mutation almost distributed in exon 7 and exon 8, eventhough this lesion is not invasive yet.…”