Nitric Oxide Synthase (NOS2/3) Expression in Head and Neck Squamous Cell Carcinomas in Correlation with Clinical Patterns

Background: Increased nitric oxide synthase (NOS) expression has been demonstrated in a number of carcinomas and is discussed to play a key role in tumor progression. The aim of this immunohistochemical study was to examine the protein expression rates of endothelial (e) NOS and inducible (i) NOS in head and neck squamous cell carcinomas (HNSCCs) and oral mucosa and to correlate the results with clinicopathologic factors (TN stage). Patients and Methods: Protein expression patterns of NOS were studied immunohistochemically (score 0-7) in 58 patients with HNSCC and 7 mucosa samples, and the results were correlated with tumor stages. Results: In oral mucosa, iNOS was only expressed in the basal epithelial layers and in macrophages, eNOS in endothelial cells and lymphocytes. In contrast, both NOS isoforms were expressed in HNSCC with preference at the tumor margins. 64% of tumor specimens demonstrated a positive eNOS immunoreactivity (score >= 3), 55% a positive iNOS immunoreactivity. NOS protein expression rates reached higher scores in tumors of patients with lymph node metastasis (N > 0; iNOS protein expression rate p < 0.05). Conclusions: HNSCCs are able to express both NOS protein isoforms in relevant amounts, and we presume that synthesized NO is able to support angiogenetic patterns and facilitate tumor progression and lymphatic spread.