Urokinase-Type Plasminogen Activator (uPA) Is a Marker of Microinvasion in High Grade Ductal Carcinoma In Situ Identified in Core Biopsy
S Khelifa, B Susnik. Feinberg School of Medicine, Northwestern University, Chicago, IL
Background: Ductal carcinoma in situ (DCIS) with microinvasion may be biologically different from DCIS without associated invasion. In order to establish potential differences we compared the imunohistochemical (IHC) expression of biomarkers in two groups, DCIS with microinvasion and DCIS without invasion.
Design: Archival core biopsies (CB) performed from 01/2006 - 04/2008 were reviewed, 19 high grade DCIS cases associated with microinvasion (M+) and a control group of 19 DCIS cases without invasion in CB or subsequent excision (M-) were identified. Cases were matched for the nuclear grade of DCIS. Clinicopathologic data were reviewed and IHC evaluation of ER, PR, HER-2, p53, Ki67, COX2, p16, Cyclin D1, uPA, uPAR and uPAI-1 was performed. Two tailed Chi square test analysis was used for statistical analysis.
Results: M+ group was upstaged to T1 in 36% of subsequent surgical excisions, while all M- cases remained Tis. M+ patients were slightly younger than the M- patients (mean age = 56.0 vs. 61.9), had similar radiologic presentation (mass vs. suspicious calcifications) and a similar frequency of birads 4C (7/19 in M+ vs. 6/19 in M-). The family history of breast cancer was more common in M- group (7/19 vs. 2/19, p: 0.056) while the personal history of breast carcinoma was only found in M+ group in 37% (86% of them contralateral). Morphologic features, including nodule formation, necrosis, periductal fibrosis and lymphocytic reaction were similar in both groups. uPA expression in DCIS cells was significantly higher in M+ group (95% M+ vs. 67% M-, p = 0.029). Although Ki-67 showed a trend for higher values in M+ group (M+ mean=27% vs. M- mean=15%), the frequency of high proliferation index (Ki67 positive in >10% nuclei) was not significantly different. The IHC results of the remaining biomarkers showed no differences between the two groups.
Conclusions: DCIS with microinvasion shows a trend for higher proliferation index and has increased uPA expression as compared to DCIS with no associated invasion. The utility of uPA as a prospective marker to identify DCIS with increased risk for progression to invasive disease should be confirmed in outcome studies.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 40, Tuesday Morning