Cytoplasmic HuR Over-expression is Associated with Increased Cyclooxygenase-2 Expression in Laryngeal Squamous Cell Carcinomas

Aims: Cyclooxygenase-2 (COX-2) is an enzyme that catalyses the synthesis of prostaglandins and is over-expressed in a variety of premalignant and malignant conditions. The human embryonic lethal abnormal vision (ELAV)-like protein, HuR, is an mRNA stability protein that can regulate COX-2 expression. Because the regulation of gene expression through the post-transcriptional modification of the mRNA stability is an important mechanism in the control of cellular growth, this study investigated the expression and cellular localisation of the HuR protein and the relationships between COX-2 and HuR in laryngeal epithelium.

Methods: The expression patterns of HuR and COX-2 in 39 laryngeal squamous cell carcinomas and paired samples of 38 normal and/or 30 dysplastic mucosa adjacent to an infiltrating carcinoma were analysed by immunohistochemistry and compared.

Results: An immunohistochemical evaluation of the specimens revealed high nuclear and cytoplasmic immunoreactivity for HuR in 39 (100%) and 26 (66.6%) of 39 lesions with laryngeal squamous cell carcinoma, 27 (90.0%) and one (3.3%) of 30 lesions with epithelial dysplasia, and 19 (50.0%) and 0 (0%) of 38 specimens with normal-appearing laryngeal epithelium, respectively. High levels of COX-2 expression were observed in 66.6% and 6.7% of laryngeal squamous cell carcinoma and epithelial dysplasia, respectively, but no COX-2 expression was detected in the normal epithelium. There was no significant correlation between HuR expression and the other clinicopathological parameters such as age, site, tumour size, or nodal status as well as histological differentiation. There was a statistically significant correlation between COX-2 immunoreactivity and the cytoplasmic HuR expression level in laryngeal squamous cell carcinoma.

Conclusions: Based on the fact that HuR in the cytoplasm indicates mRNA dysregulation of COX-2, our results suggest that their correlation plays an important role in the development and progression of laryngeal carcinoma.