Significado da expressão de p16INK4A e da perda de heterozigosidade do gene PTEN no carcinoma epidermóide bucal relacionado ao papilomavírus humano

Abstract

The p16 and PTEN genes are part of the family of tumor suppressor genes commonly associated with the inactivation of a variety of human cancers. The loss of its expression has been studied worldwide in oral squamous cell carcinoma (OSCC). In this study, we evaluated the hypothesis that p16 cooperates with inactive PTEN during OSCC pathogenesis, especially in tumor aggressiveness and proliferation. For that, 119 OSCC samples were used in which the relationship between HPV infection, p16 expression and PTEN mutations were evaluated throug himmunohistochemistry (IHC), western blot, immunofluorescence and sequencing techniques. The results of this study demonstrated that PTEN has high positivity in patients with more advanced tumor size (p < 0.01) and lymph node metastasis (p = 0.02). Statistical analysis showed that p16 expression was strongly associated with the presence of HPV (p<0.0001), but that its aberrant expression is not related to altered PTEN (p=0.52). It was also observed that 60% of the samples in stage IV (advanced stage of the tumor) were statistically associated with the presence of mutation. It is concluded that PTEN and p16 are suppressor genes that control tumor progression. In the current study, PTEN showed great erreactivity in advanced stages of the disease (greater than seven times). p16 was strongly associated with HPV, but did not show a significant association with any clinical-pathological factor analyzed. Both proteins are of great importance in the prognosis of patients. Viral presence has been shown to decrease tumor aggressiveness. Lesions in advanced stages have a shorter survival, in addition, the presence of mutation was more commonly observed in advanced stages of the disease. It was observed that smoking patients witht he absenceof p16 are significantly associated with a survival rate twice as low.