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Plasminogen Activator System Localization in 60 Cases of Ductal Carcinoma In Situ

¹ Department of Cytogenetics, Roswell Park Cancer Institute, State University of New York at Buffalo, Buffalo, New York, USA
² Department of Pathology, Kohga Community Hospital, Yaizu City, Japan
³ Department of Pathology, Roswell Park Cancer Institute, State University of New York at Buffalo, Buffalo, New York, USA
⁴ Department of Surgery, Roswell Park Cancer Institute, State University of New York at Buffalo, Elm and Carlton Streets, Buffalo, New York, USA
⁵ Department of Surgery, University of Texas Health Sciences at San Antonio, Buffalo, New York, USA

Correspondence: Address correspondence and reprint requests to: John F. Gibbs, MD; E-mail: john.gibbs{at}roswellpark.org

Background: The lack of prognostic factors in ductal carcinoma in situ (DCIS) that reliably identifies biologically aggressive tumors adversely affects optimal management. The urokinase-type plasminogen activator (uPA) system, comprised of its receptor, uPAR, and its inhibitor (PAI-1), are critical elements for tumor invasion and their expression in invasive breast cancer can predict clinical outcome. Expression of the uPA system in DCIS may be relevant in defining histological subsets of DCIS with invasive potential.

Methods: Localization of uPA, uPAR, and PAI-1 was investigated immunohistochemically in 60 DCIS tumors. FISH experiments were performed to determine whether uPA was present in cancer cells themselves or derived from stromal elements.

Results: uPA was ubiquitously expressed in the malignant ductal epithelium of 95% (57/60) of DCIS tumors studied. uPA-mRNA was detected in the malignant ductal epithelium but not the adjacent normal ductal epithelium and stromal elements. uPAR was expressed in 27% (6/22) of high-grade and 24% (9/38) of non-high-grade DCIS. In comparing coexpression, uPA and uPAR were coexpressed in only 25% (15/60) of tumors. PAI-1 was infrequently expressed in high grade (3/22) and absent in non-high-grade DCIS.

Conclusions: This study identifies the presence of uPA, uPAR, and PAI-1 in both high-grade and non-high-grade DCIS. It may be speculated that coexpression of uPA and its receptor may identify subsets of DCIS with an increased risk for progression to invasive disease. If so, then expression of uPA system components may have prognostic and therapeutic significance in DCIS.

Key Words: Urokinase-type plasminogen activator • Ductal carcinoma in situ

Abbreviations: DCIS, (ductal carcinoma in situ) • FISH, (fluorescence in situ hybridization) • IHC, (immunohistochemistry) • PAI-1, (plasminogen activator inhibitor 1) • uPA, (urinary plasminogen activator) • uPAR, (urinary plasminogen activator receptor)