Expression and Clinical Signification of Cytosolic Hyaluronan Levels in Invasive Breast Cancer

Abstract

Hyaluronic acid (HA), a high-molecular weight glycosaminoglycan, has been considered to be involved in the growth and progression of malignant tumors in several experimental studies. The objective of this work was to evaluate the cytosolic HA content in breast cancer, its possible relationship with clinicopathological tumor parameters and steroid receptor status, as well as its potential prognostic significance. Cytosolic HA levels were examined by means of immunoradiometric techniques in 850 patients with invasive breast cancer. The mean follow-up period for these patients was 55.1 months. Cytosolic HA levels ranged widely in tumors (4-59767 ng/mg protein; median: 4960). Statistical analysis showed that HA levels were significantly higher in younger patients (p=0.0001), as well as in premenopausal than in postmenopausal patients (p=0.001). HA levels were also significantly higher in ductal or lobular histological type than in other histological types (coloid, medullar or papillar types) (p=0.0001). Likewise, HA correlated significantly and positively with tumoral levels of PgR (r sub S: 0.11; p=0.001) in the all group of patients. In the subgroup of patients with ductal invasive type, HA levels were also significantly higher in well differentiated tumors and in diploid tumors. In addition, in this latter group of patients, HA levels in tumors correlated also positively and significantly with the either estrogen-inducible proteins: PgR (r sub S: 0.11; p=0.001), pS2 (r sub S: 0.117; p=0.008) and tPA (r sub S: 0.314; p=0.0001). On the other hand, significant association between HA intratumoral levels and relapse-free survival and overall survival in the overall group of patients was not found. However, high HA intratumoral levels were significantly associated with longer relapse-free survival in the subgroup of patients with ductal histological type tumors (p=0.01), as well as in those patients without any type of systemic adjuvant treatment (p=0.01). Our results suggest that high intratumoral levels of HA may be associated with tumors of favorable evolution in certain subgroups of patients with breast cancer. Thus, HA may provide additional prognostic information to that given by other biochemical markers currently used in breast cancer.