Hyaluronan expression in differentiated thyroid carcinoma

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Abstract
The extracellular polysaccharide hyaluronan (HA) controls cell migration, differentiation, and proliferation, and is supposed to contribute to the spreading of several human cancers. Little is known about the role of HA in the development and progression of differentiated thyroid carcinoma (DTC). The expression and prognostic value of HA were therefore evaluated in 204 consecutive patients with DTC. A biotinylated affinity probe specific for HA was applied to paraffin‐embedded tumour samples to assay the expression of HA in carcinoma cells and in intra/peritumoural stroma. In a majority of the samples, a high percentage (≥90%) of normal thyroid follicle epithelial cells were HA‐positive. This high percentage was also found in 80 (47%) papillary carcinomas, but only in seven (21%) follicular carcinomas (p=0.004). Age (>60 years) of the patients was significantly associated with a low percentage of HA‐positive cancer cells (p=0.013). Cancer cell‐associated HA correlated significantly with the percentage of cells expressing total CD44 and its isoforms containing exons v3 and v6 (r=0.223–0.289, p60 years) (p=0.043), and cancer‐related mortality (p=0.001). In a log‐rank univariate survival analysis, strong stromal HA staining intensity was related to DTC mortality (p=0.0007). Cancer cell‐associated HA expression did not significantly correlate with patient survival. In Cox's multivariate survival analysis, age (>60 years, p=0.0164), gender (p=0.0251), and pTNM stage (p=0.0121) were significant independent prognostic factors for DTC‐related death. These results suggest that strong stromal HA staining intensity is related to progression and unfavourable outcome in DTC patients, while the clinical factors remain more powerful in predicting DTC‐related death. Copyright © 2001 John Wiley & Sons, Ltd.
Funding Information
  • Kuopio University Hospital, Kuopio, Finland