Loss of heterozigosity analysis in oral leucoplakia and correlation with histologycal and immunohistochemical aspects

• Grant number: 12/25055-0
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2013
• End date: April 30, 2015
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Yasmin Rodarte Carvalho
• Grantee: Yasmin Rodarte Carvalho
• Host Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Estadual Paulista (UNESP). Campus de São José dos Campos. São José dos Campos , SP, Brazil

Abstract

Oral cancer is a major public health issue in Brazil and worldwide. Amongst the malignant tumors that arise in oral cavity, the epidermoid carcinoma is the most frequent one. Thousands of new cases are diagnosed each year and, despite great advances regarding its treatment, survival rates remain low and stable for decades. This is due to the fact that the majority of the lesions are not diagnosed or treated before it reaches a very advanced stage. Prevention programs that allow early detection of such lesions - even before the lesion becomes cancer - seem to be the best approach. It is accepted in the literature that clinically the epidermoid carcinoma may be preceded by potentially malignant lesions, being leucoplakia the most common among them. It is known that leukoplakias comprise a very broad variety in terms of malignant transformation. It is desirable to be able to distinguish the lesions that will progress to carcinoma from those that will not, in order to adjust treatment and follow-up for each patient. Although the degree of epithelial dysplasia is a good indicator of such potential, its histological assessment is highly subjective and a precise and reproducible classification is not available. The molecular analysis of these lesions seem to be the most accurate tool to evaluate the malignant potential, however it is only achieved using complexes methods, unfeasible in routine diagnosing. Hence, in the present study we intend to analyze molecular aspects of oral leucoplakias and correlate them with histological and immunohistochemical aspects, attempting to indicate a precise and practical that would be able to translate the molecular changes of a given lesion and, therefore, indicate its malignant potential. For that, cases diagnosed as oral leucoplakias, with or without epithelial dysplasia, will be collected from the archives of the Surgical Pathology Service at the São José dos Campos Dental School, São Paulo State University "Júlio de Mesquita Filho". The material will undergo molecular analysis by means of observation of loss of heterozygosity in genetic loci known to be important in oral carcinogenesis. Results will be correlated to immunohistochemical staining to p53, Ki-67, pRb and p16 - which are widely used proteins with well established roles in the progression of oral potentially malignant lesions - and will be also correlated to histological findings, considering epithelial cellular and architectural changes. Results will be submitted to statistical analysis and a 5% level of significance will be considered. (AU)