Banca de DEFESA: FRANCISCO JADSON LIMA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : FRANCISCO JADSON LIMA
DATA : 06/10/2016
HORA: 08:30
LOCAL: PROGRAMA DE PÓS-GRADUAÇÃO EM PATOLOGIA ORAL
TÍTULO:

STUDY OF CLIC4 EXPRESSION AND ASSOCIATED PROTEINS IN ACTINIC CHEILITIS AND SQUAMOUS CELLS CARCINOMA OF THE LOWER LIP

PALAVRAS-CHAVES:

Actinic cheilitis. Squamous cell carcinoma of the lower lip. Tumor progression. CLIC4

PÁGINAS: 76
GRANDE ÁREA: Ciências da Saúde
ÁREA: Odontologia
SUBÁREA: Clínica Odontológica
RESUMO:

Lower lip carcinogenesis is mainly induced by chronic exposure to the sun's ultraviolet rays, but many of the molecular aspects involved in this process are still not understood.The protein chloride intracellular channel 4 (CLIC4) is a chloride channel regulated by p53 protein and tumor necrosis factor α (TNF-α), which has been linked to an increase in transforming growth factor-β level (TGF-β), with skin carcinogenesis, and differentiation of fibroblasts into myofibroblasts. Hence, this study aimed to analyze and compare the immunohistochemical expression of CLIC4, p53, TGF-β, TNF-α and α-smooth muscle actin (α -SMA) in actinic cheilitis (AC) and in theinvasive front of squamous cell carcinomas of the lower lip (SCCLL), as well as to verify the relationship of these proteins with each other and with clinical and morphological features of the lesions.The sample consisted of 50 cases of ACs and 50 SCCLLs with clinical data, which were initially submitted to morphological study for grading their risk of malignant transformation (binary system) and histological grade of malignancy (Bryne, 1998), respectively. All cases were submitted to the immunoperoxidase method using anti-CLIC4, anti-p53, anti-TGF-β, anti-TNF-α and anti-α-SMA antibodies, which were subjected to semi-quantitative analysis, exceptp53, which was initially analyzed quantitatively. Comparisons of immunostainings within clinical and morphological parameters were performed by the Mann-Whitney U test and Spearman correlation coefficient was calculated to evaluate correlations between proteins. The significance level of 5% was adopted.Nuclear expression of CLIC4 and TGF-β was increased in low-risk ACs when compared with high risk group (p<0.0001), whereas cytoplasmic CLIC4,p53 and TNF-α exhibited higher expression in high-risk ACs (p<0.05).With regard to the clinical and morphological characteristics of SCCLLs, the CLIC4 expression in the cytoplasm of tumor cells was higher in cases presenting lymph node metastasis, cases with more advanced clinical stages or with high malignancy grade (p = 0.005; p = 0.029; p <0,0001). The p53 expression was higher in SCCLLs with high grade of malignancy, than in low grade cases (p = 0.001) and TGF-β decreased significantly according to the advancement of clinical stage and histological grade of the tumors (p< 0,05). There was no significant difference in α-SMA and TNF-α expression when comparing clinical parameters and histological grading of SCCLLs. Comparing the two lesions, AC sexhibited an increased expression of CLIC4 (in the nucleus, or in the nucleus and cytoplasm) and TGF-β compared with SCCLLs (p <0.0001). In contrast, there was an increase in cytoplasmic CLIC4 and α-SMA staining in the carcinomas when compared to ACs (p<0.0001). In the ACs studied, a negative correlation was observed between nuclear CLIC4 expression with cytoplasmic CLIC4 (r = -0.554; p<0.0001), and between the TGF-β and α-SMA staining (r = -0.309; p = 0.029). In carcinomas, p53 expression showed positive correlation with TNF-α (r = 0.528, p = 0.0001) and α-SMA (r = 0.435; p = 0.002), while the latter two proteins exhibited a weak direct correlation with each other (r = 0.293; p = 0.039).Our results suggest that a change in the pattern of nuclear to cytoplasmic expression for CLIC4 is involved in the lip carcinogenesis process, accompanied by changes in p53, TGF-β, TNF-α, and α-SMA expression, althoughnot always, these findings are related to the morphological and clinical aspects of ACs and SCCLLs.

MEMBROS DA BANCA:
Presidente - 2492713 - ERICKA JANINE DANTAS DA SILVEIRA
Interno - 346077 - LELIA BATISTA DE SOUZA
Externo à Instituição - MANOELA DOMINGUES MARTINS - UFRGS
Externo à Instituição - MANUEL ANTONIO GORDON NUNEZ - UEPB
Interno - 350484 - ROSEANA DE ALMEIDA FREITAS