Abstract
The HIF-1 transcriptional complex is responsible for controlling transcription of over 100 genes involved in cell hypoxia response. HIF-1alpha subunit is stabilized in hypoxia conditions, creating the HIF-1 nuclear transcription factor. In inflammatory cells, high HIF-1alpha expression induces lymphocytic immunosuppression, decreasing tumoral antigen recognition, which promotes tumor growth. The present work investigated the relationship between HIF-1alpha expression in lymphocytes populating the intratumoral and peritumoral region of 56 patients with oral cancer. Our data indicates a prognostic value for this expression. High HIF-1alpha expression in peritumoral inflammatory cells is significantly related to worse patient outcome, whereas high expression in the intratumoral lymphoid cells correlates with a better prognosis. A risk profile indicating the chance of disease relapse and death was designed based on HIF-1alpha expression in tumoral inflammatory cells, defining low, intermediate and high risks. This risk profile was able to determine that high HIF-1alpha expression in peritumoral cells correlates with worse prognosis, independently of intratumoral expression. Low HIF-1alpha in tumor margins and high expression in the tumor was considered a low risk profile, showing no cases of disease relapse and disease related death. Intermediate risk was associated with low expression in tumor and tumor margins. Our results suggest that HIF-1alpha expression in tumor and peritumoral inflammatory cells may play an important role as prognostic tumor marker.
Highlights
Head and neck cancer is a significant cause of mortality and morbidity worldwide, presenting approximately 600,000 new cases yearly [1], reaching the sixth leading cause of death by cancer [2]
High HIF-1alpha expression in lymphoid peritumoral cells was correlated with worse disease-free and disease-specific survivals (p = 0.028 e p = 0.008, respectively)
Present in several cancer types, have a clinical significance better understood in breast and colorectal tumors [20,221], being interpreted by the pathologist as prognostic predictive factors
Summary
Head and neck cancer is a significant cause of mortality and morbidity worldwide, presenting approximately 600,000 new cases yearly [1], reaching the sixth leading cause of death by cancer [2]. Tumor histopathological results have been considered supplementary prognostic data, helping in the therapeutic decision making [5]. Among these results, positive tumor margins have been predictive of disease relapse, frequently influencing the therapeutic decision [6]. Positive tumor margins have been predictive of disease relapse, frequently influencing the therapeutic decision [6] Another important information resulting from the histopathological analysis is the presence of inflammatory cells in the intratumoral region, the role of this infiltrate is still controversial
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