Presence and Quantity of COX-2 in Lymph Node Metastases of Patients with Head and Neck Cancer

Introduction Head and neck cancer represents the sixth most common cancer worldwide with an incidence of approximately 630,000/year [1]. More than 95% of these tumors are squamous cell carcinomas (SCC). Despite advances in the major therapeutic areas, such as surgery, radiotherapy and chemotherapy, the survival rates for patients suffering from this disease have not significantly improved within the past decades [2]. Therefore, identifying new molecular targets in head and neck squamous cell carcinomas (HNSCC) might contribute to improving cancer treatment and patients’ overall prognosis. Cyclooxygenases (COX) catalyze the synthesis of prostanoids from arachidonic acid. There are two isoforms of COX, namely COX-1 and COX-2 [3]. COX-1 is constitutively expressed in various cells, whereas COX-2 is an inducible enzyme. The induction of the COX-2 gene is stimulated by various factors, such as cytokines, oncogenes and carcinogens. It is reported to be predominantly induced and activated in numerous pathological conditions, such as inflammation and cancer [4,5]. It has been revealed from various studies that COX-2 is overexpressed in numerous human tumors, including HNSCC [6-8]. Further, COX-2 seems to play an important role in carcinogenesis and tumor progression, as it has been shown to be upregulated in transformed cells, premalignant as well as malignant lesions [9]. In oral squamous cell carcinoma, it has been shown by Pandey et al., that COX-2 expression has been significantly upregulated in OSCC compared to normal mucosa and oral dysplasia [10]. Further, COX-2 has been shown to promote tumor progression by inducing various pathways in critical stages of malignant disease [11]. Its overexpression and activity stimulate cell division, angiogenesis and metastases [12,13]. Studies suggest that COX-2 contributes to tumor progression by modulating the immune system to reduce anti-tumor immune responses [14,15]. Also, it has been suggested to act on tumor cells by promoting their mitotic activity and subsequently aid the conversion of premalignancy to invasive tumors [16]. Further, COX-2 has been described to induce angiogenic factors, such as vascular endothelial growth factor (VEGF) and fibroblastic growth factor, and therefore promotes tumor angiogenesis, tumor cell migration, and the formation of local and distant metastases [17,18]. Overexpression of COX-2 in primary tumor tissues has been shown to correlate negatively with patients’ outcome and positively with tumor progression and recurrence rates in numerous tumors, including HNSCC [19,20]. SciTeMed Publishing Group Archives of Otorhinolaryngology Head & Neck Surgery ORIGINAL ARTICLE