Hyaluronan in peritumoral stroma and malignant cells associates with breast cancer spreading and predicts survival

Hyaluronan (HA) is an extracellular matrix polysaccharide that promotes cel l migration through its cell surface receptors and by effecting changes in the physical environment, HA expression is frequently increased in malignan t tumors, whereas its association with the invasive potential and patient o utcome in breast cancer has not been reported. The localization and signal intensity of HA. was analyzed in 143 paraffin-embedded tumor samples of hum an breast carcinoma using a biotinylated HA-specific probe. In the immediat e peritumoral stroma, HA signal was moderately or strongly increased in 39% and 56% of the cases, respectively. Normal ductal epithelium showed no HE, whereas in 57% of the tumors at least some of the carcinoma cells were HA positive. The intensity of the stromal HA signal and the presence of cell-a ssociated HA were both significantly related to poor differentiation of the tumors, axillary lymph node positivity, and short overall survival of the patients. In Cox's multivariate analysis, both the intensity of stromal HA signal alone and that combined with the HA positivity in tumor cells were i ndependent prognostic factors for overall survival. These results suggest t hat HA is directly involved in the spreading of breast cancer and may offer a potential target for new therapies.