Increased hyaluronan content and stromal cell CD44 associate with HER2 positivity and poor prognosis in human breast cancer

Abstract

Previous in vitro studies have suggested interactions between hyaluronan (HA), CD44 and HER2. We have studied the expression of HA and CD44 in a material of 278 breast cancer cases, half of which were HER2-positive. Intense stromal HA staining was associated with HER2 positivity, large tumor size, lymph node positivity, hormone receptor negativity, poor differentiation, a high body mass index, increased relapse rate and shortened overall survival. Among the 139 HER2-positive cases, the relapse rate was associated with the intensity of stromal HA staining as most of the relapses occurred in the cases with intense stromal HA staining. The presence of HA in the carcinoma cells was related to the frequency of relapses as none of the patients without HA in carcinoma cells experienced a relapse, whereas 33.3% of those with a high percentage of HA-positive carcinoma cells suffered a relapse. CD44 positivity in carcinoma cells was related to poor differentiation, postmenopausal status and triple negative breast carcinoma. CD44 positivity in stromal cells was associated with HER2 positivity, large tumor size, hormone receptor negativity, poor differentiation, increased relapse rate and shortened overall survival. The association between HER2 positivity and intense stromal HA staining indicates that HA could be one of the factors involved in the unfavorable outcome of HER2-positive patients. This study also suggests that HA in breast carcinoma cells and CD44 in stromal cells may have clinical significance. What's new? Elevated levels of HER2 occur in more than one-fifth of breast cancers and in vitro appear to result from interactions between the transmembrane receptor CD44 and hyaluronan, a component of the extracellular matrix. New data on these interactions reveals an association between increased hyaluronan and HER2-positivity, characterized in part by intense stromal hyaluronan staining related to obesity and disease relapse. The data suggest that hyaluronan and CD44, which was also linked to relapse, may be of clinical significance in determining breast cancer prognosis. © 2012 UICC.