Estudo da perda de heterozigosidade em regiões de genes supressores de tumor e sua associação com alterações morfológicas e grau de displasia epitelial em leucoplasias bucais

Abstract

Oral leukoplakia is the main potentially malignant lesions of the mouth. The genetic instability in tumor suppressor genes may be related to the biological behavior and malignant transformation of oral leukoplakia. The aim of this study was investigate the loss of heterozygosity in regions related to tumor suppressor genes in oral leukoplakia and its association with cytological and architectural abnormalities of epithelium, as well as with histopathological grade of dysplasia and clinical-pathological data. Loss of heterozygosity in 3p, 9p, 11p, 11q and 17p was assessed by analysis of microsatellite markers (D3S1234, D3S1300, D3S1029, D3S1293, D9S157, D9S162, D9S171, D11S1369, D11S1883, AFM238WF2 and P53). From the archives were selected 17 cases of leukoplakia that had at least two biopsies at the same anatomical site. Histopathologically, the samples were graded according to the World Health Organization criteria. 20 samples showed mild epithelial dysplasia; 10 moderate epithelial dysplasia; 2 severe epithelial dysplasia; and 2, oral squamous cell carcinomas. Loss of heterozygosity was observed in 30 samples in at least one marker, except from D3S1029. The markers related to chromosome region 3p, 9p, 11q and 17p (D3S1293 D9S157, D9S162, D9S171, D11S1369 and P53) showed higher frequency of allelic loss exceeding 40%. Additionally, loss of heterozygosity at markers D9S171, D9S162 and P53 was associated with cytological and architectural abnormalities of epithelium (p<0.05). Furthermore, high frequency of allelic loss was associated with severe epithelial dysplasia and carcinomas (p<0.05). The samples of carcinomas showed LOH at regions 3p, 9p, 11q and 17p, simultaneously, unlike the profile found in majority of leukoplakia. The results of this study support that loss of heterozygosity in regions of tumor suppressor genes represent a frequent event in oral leukoplakia and may be associated with the cytological and architectural abnormalities of epithelial dysplasia. However, LOH of chromosome regions 3p, 9p, 11q, 11p and 17p may be not sufficient to predict the increase of degree of epithelial dysplasia and malignant transformation of oral leukoplakia.