Expression of Ki-67 and P16 INK4a in chemically-induced perioral squamous cell carcinomas in mice.

OBJECTIVE: to evaluate the influence of Ki-67 and P16INK4a proteins immunohistochemical expressions on the clinical and morphological parameters of perioral squamous cell carcinoma induced with 9,10-dimethyl-1,2-benzanthracene (DMBA) in mice. METHODS: we topically induced the lesions in the oral commissure of ten Swiss mice for 20 weeks, determining the time to tumors onset and the average tumor volume up to 26 weeks. In histopathological analysis, the variables studied were histological malignancy grade and the immunohistochemical expression of Ki-67 and P16INK4a proteins. The correlation between variables was determined by application of the Spearman correlation test. RESULTS: the mean time to onset of perioral lesions was 21.1 +/- 2.13 weeks; mean tumor volume was 555.91 +/- 205.52 mm3. Of the induced tumors, 80% were classified as low score and 20% high score. There was diffuse positivity for Ki-67 in 100% of lesions - Proliferation Index (PI) of 50.1 +/- 18.0. There was a strong direct correlation between Ki-67 immunoreactivity and tumor volume (R = 0.702) and a low correlation with the malignancy score (R = 0.486). The P16INK4a protein expression was heterogeneous, showing a weak correlation with tumor volume (R = 0.334). There was no correlation between the immunohistochemical expression of the two proteins studied. CONCLUSION: in an experimental model of DMBA-induced perioral carcinogenesis, tumor progression was associated with the tumor proliferative fraction (Ki-67 positive cells) and with tumor histological grading, but not with P16INK4a expression. OBJETIVO: avaliar a influencia da expressao imuno-histoquimica das proteinas Ki-67 e p16INK4a sobre parametros clinico-morfologicos em carcinomas espinocelulares periorais quimicamente induzidos com 9,10-dimetil-1,2-benzantraceno (DMBA) em modelo murino. METODOS: as lesoes foram induzidas topicamente na comissura labial de dez camundongos Swiss durante 20 semanas, sendo determinado o momento de surgimento dos tumores e volume tumoral medio ate 26 semanas. Na analise histopatologica, as variaveis estudadas foram gradacao histologica de malignidade tumoral e expressao imuno-histoquimica das proteinas Ki-67 e p16INK4a. A correlacao entre as variaveis estudadas foi determinada pela aplicacao do teste de correlacao de Spearman. RESULTADOS: o tempo medio de surgimento das lesoes periorais foi 21,1+/-2,13 semanas. Volume tumoral medio foi de 555,91+/-205,52mm3. Dos tumores produzidos, 80% foram classificados como de baixo escore e 20%, alto escore. Evidenciou-se positividade difusa para Ki-67 em 100% das lesoes - indice de marcacao (PI) de 50,1+/-18,0. Verificou-se correlacao direta forte entre a imunoexpressao do Ki-67 e o volume tumoral (R=0,702) e fraca correlacao com o escore de malignidade (R=0,486). A expressao da proteina p16INK4a foi heterogenea, mostrando fraca correlacao com o volume tumoral (R=0,334). Nao houve correlacao entre a expressao imuno-histoquimica das duas proteinas estudadas. CONCLUSAO: Em modelo experimental de carcinogenese perioral DMBA-induzida, a progressao tumoral esta associada a fracao proliferativa do tumor (celulas ki-67 positivas) e com a gradacao histologica tumoral, porem nao com a expressao da p16INK4a.