Reduced expression of hyaluronan is a strong indicator of poor survival in oral squamous cell carcinoma

Abstract

Several malignant tumours accumulate hyaluronan (HA), a matrix component suggested to promote cancer cell growth and migration. The expression and prognostic value of HA was analysed in a cohort of 151 oral squamous cell carcinoma (SCC) patients with adequate archival tumour material and follow-up data. The tumour samples were stained using a biotinylated HA-specific probe. Normal squamous epithelium showed a strong and homogeneously distributed staining for HA. The most superficial layers were HA-negative. In moderate ( n=11) and high grade ( n=16) dysplasias an irregular HA staining was observed around invasive cancer. Malignant transformation in oral squamous cell epithelium changed the staining toward irregular with focal reduction of HA. The well ( n=92) or moderately differentiated ( n=47) carcinomas had a strong HA staining intensity. In poorly differentiated tumours ( n=12) the HA staining was weaker and mainly intracellular. The stromal tissue showed usually moderate ( n=69) or strong ( n=67) HA staining intensity with no statistically significant correlation with the degree of tumour differentiation. At the end of the follow-up (median 52 months) 66 (43%) patients had died because of an oral SCC. A significant difference in overall survival (OS) and disease free survival (DFS) ( P=0.0002 and 0.0020, respectively) was noticed between the patients with the different epithelial staining patterns for HA. The reduction of HA staining was associated with poor survival. In Cox's multivariate analysis HA staining was a significant independent predictor of OS ( P=0.011) and DFS ( P=0.013). These results suggest that HA is a prognostic marker in oral squamous cell carcinoma.