Urokinase Plasminogen Activator Receptor (uPAR): A Potential Indicator of Invasion for In Situ Breast Cancer.
Urokinase plasminogen activator (uPA) and its cellular receptor (uPAR) are important mediators in the cellular process of cancer invasion and metastasis. Ductal carcinoma in situ (DCIS) is classified by lack of invasion into the adjacent stroma, yet definitive histologic features have not been identified to indicate the propensity for cellular invasion. Therapy for DCIS remains controversial because of the probability for recurrence. We hypothesized that uPA and uPAR may represent new predictors for recurrence of DCIS. Tissue specimens were obtained from 10 normal, 10 hyperplasia, and 70 patients with DCIS. Representative sections of the regions were mounted and stained by immunohistologic techniques using mouse anti-human uPA and uPAR antibodies. Stain intensities were assessed by densitometry image analysis. Gray scale values for in situ patients were compared to normal averages to determine whether staining intensities were normal or significantly higher (p < 0.05) than normal. DCIS tissues were heterogeneous for stain intensities of uPA and uPAR. Patients with high stain intensities for uPAR (28/70 = 40%) correlated with a higher recurrence rate (15/28 = 54%) than with patients having high stains for uPA (19/70 = 28% with 17/50 = 34% recurrence). In addition, patients with combined high stains for uPA and uPAR (11/19 = 60%) showed a recurrence rate of 55% compared to high uPA/normal uPAR with 0% recurrence. Immunohistologic evaluation of DCIS for uPAR, alone and in combination with uPA, significantly correlates with recurrence of invasive breast carcinoma. Evaluation of uPAR among DCIS lesions may provide a new prognostic indicator for recurrence of breast carcinoma.
Guyton
Daniel P.
DP
Department of Surgery and Kenneth Calhoun Research Laboratory, Akron General Medical Center, Akron, Ohio, and Department of Surgery, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio.
Evans
Douglas M.
DM
Sloan-Stakleff
Kimberly D.
KD