Classical dysplasia classification is subjective and has very important limitations. With this doctoral thesis we try to demonstrate the usefulness of some molecular biomarkers that could improve the obtained information from the routine histopathological analysis in order to detect the risk of malignant transformation. This thesis is divided in two different parts: First Part: This part has been carried out at the Faculty of Medicine in Geneva and will be presented with two papers to opt for the mention of European doctoral thesis. On the first paper the more important aspects regarding Oral Lichen Planus natural dynamic evolution are reviewed and the different stages of activity are presented. On the second paper the aim was to analyse the expression of hsp27 in 36 specimens of OLP lesions that were divided into three groups (G1, G2 and G3) depending on the activity and 10 of healthy patients by immunohistochemistry (staining intensity and percentage of stained cells) and results of staining were compared between the different groups. Gender, age and anatomical location were also studied. The results show that in the basal layer, an increase of hsp27 expression in both G2 and G3 was observed when compared to G1 and control group. In contrast, a decrease of hsp27 expression in the superficial layer was observed in all groups when compared to control group. The increased expression of Hsp27 in the basal layer observed during the OLP evolution and the less staining in the superficial layers in all cases of OLP suggest that hsp27 may have a role in the OLP pathogenesis. Second part: This part has been carried out at the Complutense University of Madrid and at the General University Hospital Gregorio Marañón in Madrid. The aim was to analyse if the expression of the histo-blood group antigens A, B, Lewis a, b, x, y and the Heat Shock Proteins (Hsps) hsp27, 60,70 and 90 was different depending on the type of histological lesion analysed (Oral Squamous Cell Carcinoma (OSCC), areas next to the OSCCs and oral leukoplakias with different grade of dysplasia and normal mucosa). By means of immunohistochemistry, the expression of those antigens was analysed in 22 OSCC, 21 normal mucosa, 34 areas next to the OSCC and in 29 oral leukoplakias. Before any analysis, it was performed a validation for the semiquantitative method of scoring. Results show different patterns of expression with the antigens analysed depending on the type of histological lesion. In this sense the most 6 relevant events were the loss of expression of the histo-blood group antigen A in Oral Squamous Cells Carcinomas (OSCCs), the aberrant expression of group B detected in an patient with OSCC belonging to group A and the total loss of hsp90 expression in all groups except for the control group. It was also detected a variable expression of the antigens analysed depending on the grade of dysplasia. Some associations were detected between the positive or negative expression of some of the antigens analysed and certain variables. Belonging to group B and suffering from a future tumour were the more influential variables in the survival analysis. Hsp90 demonstrated to be the more capable variable to discern between the four main groups analysed in this study. We conclude this study asking for standardized protocols to homogenize the obtained results from the different studies or to make them more comparable.
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