Relação da infecção pelo HPV e dos marcadores anexina-A1 e P53 no câncer de orofaringe

Abstract

Oropharyngeal cancer is a prevalent disease with high morbidity and mortality. It has traditionally been associated with smoking and alcohol consumption. However, its occurrence is increasing in younger populations and in people without such risk factors. Infection caused by human papillomavirus (HPV) is often found in these tumors and it is supposed that the virus can have a causal role in its emergence. In addition, several molecular markers have been studied in head and neck tumors. Among them, we highlight the proteins p53 and annexin-A1 (ANXA1). The latter has a differential expression in various types of cancers and there is growing evidence that it may be involved in the carcinogenic process. In this study, we investigated the prevalence of HPV infection and its relationship with the expression of p53 and ANXA1 in a group of patients with oropharyngeal cancer. MATERIALS AND METHODS We analyzed tissue samples from patients with squamous cell carcinoma of the oropharynx and their non-neoplastic epithelial margins. We also used oropharyngeal epithelial tissue samples from individuals without head and neck cancer as controls. The evaluation of the presence of the HPV genome in cancer samples was performed by chromogenic in situ hybridization with probes that identified subtypes 16/18 and 31/33. The expression of p53 and ANXA1 and its phosphorylated forms at residues Ser27 and Tyr21 was evaluated by immunofluorescence. The quantification of the expression of ANXA1 was done by measuring the mean optical density. RESULTS The prevalence of HPV genome was 59.1%. Expression of ANXA1 in the epithelial margin of tumor patients was similar to that observed in samples from control patients. We demonstrated a decreased expression of p53 in HPV+, compared to HPV- tumors. ANXA1 expression was reduced in tumors when compared to epithelial margins and controls. We also noted a reduction in ANXA1 phosphorylated at Tyr21 in tumors. However, the expression of ANXA1 phosphorylated at Ser27 was increased in the epithelial margin of HPV+ cases. CONCLUSION Our results confirm the high prevalence of HPV in oropharyngeal cancer. Reduction of p53 expression in HPV+ tumors reinforces the oncogenic ability of the virus even without accumulation of mutated p53. We also observed a hypoexpression of ANXA1 in oropharyngeal cancer regardless of HPV status. Elevated ANXA1 phosphorylated at Ser27 in the epithelial margin of HPV+ tumors may indicate an activation of the epithelium in response to the infectious agent. On the other hand, the reduced expression of ANXA1 phosphorylated at Tyr21 in tumors may be related to its use by the epidermal growth factor receptor (EGFR) during tumor proliferation.