Immunohistochemical study of PI3K-AKT-mTOR pathway expression in potentially malignant oral lesions

Abstract

Leukoplakia is the most common malignant lesions, affecting approximately 2% of the population. Oral leukoplakia is a clinical descriptive term for a predominantly white lesions of the oral mucosa that cannot be removed by scraping and cannot be classified clinically or diagnostically as any other disease entity, and that present a questionable risk. Thus, the study of those lesions can give support to the knowledge of oral carcinogenesis. Diagnosis using antibodies, alone or in combination, have been recognized as promising for use as molecular markers in the study of epithelial dysplasia. The PI3K and AKT pathway interfere with growth control and cell survival, proliferation and angiogenesis in various cell types involved in carcinogenesis and are inhibited by the tumor suppressor gene PTEN. These proto-oncogenes have been associated with the progression from dysplasia to carcinoma. Oral mucosa samples from 120 cases clinically diagnosed as leukoplakias will be retrieved. Those will be separated into four groups: no dysplasia, and epithelial dysplasia graded as mild, moderate and severe, 30 cases of squamous cell carcinoma and 30 samples from reactive lesions as the control group. Later the lesions will be also classified in the new binary system into low grade and high grade of malignant transformation. Clinical information regarding sex and age of patient, habits, location, appearance and duration of the lesion will be compiled. Tests will be performed using immunohistochemistry and antibodies will be used as follows: p-mTOR, 4EB-P1, eIF4E, p-AKT, and Pten , p27, c-Jun, pc-Jun e JAB1. Three pathologists previously calibrated will observe the slides, and the cells will be counted and represented in percentage. The expression of different antibodies will be evaluated qualitatively as positive and negative. The findings obtained in the specimens of groups will be compared to specimens of other groups. (AU)