THE OVEREXPRESSION OF RHAMM, A HYALURONAN-BINDING PROTEIN THAT REGULATES RAS SIGNALING, CORRELATES WITH OVEREXPRESSION OF MITOGEN-ACTIVATEDPROTEIN-KINASE AND IS A SIGNIFICANT PARAMETER IN BREAST-CANCER PROGRESSION

RHAMM is an oncogene that regulates signaling through ras and controls mitogen-activated protein kinase [extracellular signal-regulated prot ein kinase (ERK)] expression in embryonic murine fibroblasts. ERK is a dual-specificity kinase that controls expression of proteins relevant to tumorigenesis, proliferation, and motility, To assess whether RHAM M and ERK are involved in human breast tumor progression, we examined RHAMM, ras, and ERK expression in two cohorts of breast cancer patient s using reverse transcription-PCR and immunocytochemistry. We show tha t overexpression of RHAMM in primary tumors of two patient cohorts was significantly prognostic of poor outcome in breast cancer progression . Furthermore, RHAMM overexpression occurred within subsets of tumor c ells in the primary tumor, and this staining pattern was associated wi th lymph node metastases. The metastases exhibited a significantly hig her level of staining for RHAMM than did the primary tumor, RHAMM expr ession strongly correlated with overexpression of both ras and ERK, al though overexpression of either of these two signaling molecules was n ot by itself a prognostic indicator, These results identify a new para meter that is involved in lymph node metastasis of primary breast canc ers and suggest that quantification of RHAMM overexpression may be a u seful prognostic indicator for breast carcinoma progression.