Estudos dos aspectos clínico-patológicos e da imunoexpressão das proteínas APE1 e XRCC1 em uma série de leucoplasias orais

Abstract

Background: Oral leukoplakia (OL) is the most frequent oral potentially malignant disorder in dental practice. At histopathological examination, most of the OLs exhibit histological changes that may or may not be associated with epithelial dysplasia (ED), however, there is no consensus if the presence of ED is indicative of malignant transformation. DNA repair is an important genetic mechanism related to carcinogenesis. In this process, specific genes and proteins act in the detection and removal of the damage with subsequent DNA repair, highlighting in this research the base excision repair (BER) pathway which APE1 and XRCC1 proteins act. Thus, the aim of this study was to verify if the APE1 and XRCC1 proteins are associated with clinicopathological features. Methods: Forty patients diagnosed with OL were selected, clinical data were collected in the clinical records and during each patient’s follow-up. For each case, morphological analysis was performed, in case where there was ED the epithelial dysplasia grading according with the World Health Organization was performed. The immunohistochemical expression of APE1 and XRCC1 was evaluated in 24 cases of OL and in six cases of normal oral mucosa (NOM). A semiquantitative analysis was performed, where the cases were classified as negative immunoexpression (0-10% of positive cells), low (11-50% of positive cells) and high immunoexpression (> 50% of positive cells). Pearson’s chi-square and Fisher's exact tests were performed to determine the association between protein expression and clinicopathological features (significance of p≤0.05). Results: Of the 40 cases of OL 65% were female with a mean age of 58 years. Thirty patients had tobacco consumption habit. Tongue was the most affected location (27.5%). Thirty-two cases presented homogeneous lesions while 60% and 41.2% of the cases showed multiple lesions and lesions recurrence, respectively. A significant association was observed in the cases graded as moderate/severe ED with the non-homogeneous clinical aspect (p=0.039). APE1 and XRCC1 proteins showed high expression in NOM and OL independent of the presence or absence of epithelial dysplasia. APE1 demonstrated nuclear immunostaining in 60% of cases graded as moderate or severe epithelial dysplasia (p=0.005). Conclusions: The non-homogeneous clinical aspect of OL was a strong indicator of the presence of moderate/severe epithelial dysplasia. The APE1 and XRCC1 proteins do not appear to be related to molecular processes involved in the development and with the clinicopathological features of oral leukoplakias.