Georgette G Chan

The purpose of this study was to determine whether cyclooxygenase-2 (COX-2) was overexpressed in squamous cell carcinoma of the head and neck (HNSCC). Quantitative reverse transcription-PCR, immunoblotting, and immunohistochemistry were used to assess the expression of COX-2 in head and neck tissue. Mean levels of COX-2 mRNA were increased by nearly 150-fold in HNSCC (n = 24) compared with normal oral mucosa from healthy volunteers (n = 17). Additionally, there was about a 50-fold increase in amounts of COX-2 mRNA in normal-appearing epithelium adjacent to HNSCC (n = 10) compared with normal oral mucosa from healthy volunteers. Immunoblotting demonstrated that COX-2 protein was present in six of six cases of HNSCC but was undetectable in normal oral mucosa from healthy subjects. Immunohistochemical analysis showed that COX-2 was expressed in both HNSCC and adjacent normal-appearing epithelium. Taken together, these results suggest that COX-2 may be a target for the prevention or treatment of HNSCC.

ABSTRACT Cyclooxygenase (COX) catalyzes the formation of prostaglandins (PG) from arachidonic acid. A large body of evidence has accumulated to suggest that COX‐2, the inducible form of COX, is important in carcinogenesis. In this study, we determined whether (1) COX‐2 was overexpressed in squamous cell carcinoma of the head and neck (HNSCC) and whether (2) retinoids, a class of chemopreventive agents, blocked epidermal growth factor (EGF)‐mediated activation of COX‐2 expression. Levels of COX‐2 mRNA were determined in 15 cases of HNSCC and 10 cases of normal oral mucosa. Nearly a 100‐fold increase in amounts of COX‐2 mRNA was detected in HNSCC. By immunoblot analysis, COX‐2 protein was detected in 6 of 6 cases of HNSCC but was undetectable in normal mucosa. Because retinoids protect against oral cavity cancer, we investigated whether retinoids could suppress EGF‐mediated induction of COX‐2 in cultured oral squamous carcinoma cells. Treatment with EGF led to increased levels of COX‐2 mRNA, COX‐2 protein, and synthesis of PG. These effects were suppressed by a variety of retinoids. Based on the results of this study, it will be important to establish whether newly developed selective COX‐2 inhibitors are useful in preventing or treating HNSCC. Moreover, the anticancer properties of retinoids may be due, in part, to inhibition of COX‐2 expression. Combining a retinoid with a selective COX‐2 inhibitor may be more effective than either agent alone in preventing cancer of the upper aerodigestive tract.

INTRODUCTION: Head and neck cancers remain one of the top twenty cancers in Singapore for the past decade. Squamous cell carcinoma (SCC) is the commonest histology. Our aim was to obtain local figures on treatment modalities and survival outcomes. METHODS: This is a ten-year retrospective study of all head and neck SCC (HNSCC) cases operated from 1988-1998 at the Department of General Surgery, Singapore General Hospital. RESULTS: We treated 242 patients with HNSCC. Median follow-up time was 31 months. Seventy percent of these patients presented with Stage III/IV disease. The 3 most commonly occurring sites of HNSCC are 79 (33%) tongue, 68 (28%) rest of oral cavity and 36 (15%) larynx. The majority of the patients underwent surgical resection with reconstruction and adjuvant radiotherapy. The recurrence-free survival at 2 and 5 years are 60% (95% CI) and 52% (95% CI). The overall survival at 2 and 5 years are 70% (95% CI) and 55% (95% CI). The overall survival for Stages I-IV at 2 years' follow-up were 97%, 83%, 66% and 60% respectively and at 5 years' follow-up, were 83%, 71%, 59% and 38% respectively. CONCLUSIONS: HNSCC treated in this department over the last decade have resulted in survival rates that are comparable with those reported from international cancer centres and an improvement over previous local experience.