Expressionof urokinase plasminogen activator (UPA) in malignant and benign breast tissue:analysis by quantitative RT-PCR assays

M36 EXPRESSION OF UROKINASE PLASMINOGEN ACTIVATOR (UPA) IN MALIGNANT AND BENIGN BREAST TISSUE: ANALYSIS BY QUANTITATIVE RT-PCR ASSAYS Ceccarelli Francesca, Fuso Andrea, Civitelli Liana, Ranieri Ersilia, Pagni Paola, Caprio Giuliana, Rengo Mario, Scarpa Sigfrido Surgical Department ‘‘Pietro Valdoni’’, University of Rome ‘‘La Sapienza’’, Rome, Italy Background: degradation of extracellular matrix by proteolytic enzymes is an important step for tumour invasion and metastasis; uPA is a cornerstone in this process and it plays an essential role in migration and cell adhesion. Patients and methods: the expression of uPA mRNA was examined in 4 breast cancer samples (2 ductal invasive breast cancer and 2 lobular invasive breast cancer) and 4 benign breast lesions (2 fibroadenoma and 2 typical hyperplasia). We compared these values with uPA expression of good health women leucocytes (arbitrary value = 1). We used RT Real Time-PCR assays; uPA expression levels were normalized to the expression level of housekeeping gene 18S. In breast cancer group, all women were in postmenopausal state with median age of 67,25 years. Benign group women were relatively younger, with median age of 52 years. Result: uPA expression was significantly elevated in malignant samples when compared to the benign lesions group (5,55-folds vs 3,48-folds). Elevated uPA mRNA levels were associated with negative steroid hormone receptor status (ER- = 11,72-folds vs ER+ = 2,77-folds), high values of Ki67 (10% = 1,43-folds vs 70%= 13-folds) and high clinical stage at diagnosis, with 13-folds increase in inflammatory carcinoma. Conclusion: these data indicate that uPA is up-regulated in malignant samples and are consistent with its role in determining invasive potential and poor prognosis in breast