Abstract P2-10-38: Prognostic factors uPA/PAI-1: measurement in core needle biopsies

Abstract

Abstract Background: The urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 are validated as prognostic factors at the highest level of evidence within the node-negative group of breast cancer patients (Harris L et al., JCO 2007; 25:5287). Usually, patients receive a core-needle biopsy before surgery. A prior feasibility study showed that the method of sampling (ex vivo from the surgical specimen using a small core needle or the larger excision specimen) doesn't influence the uPA and PAI-1 results (Thomssen et al., J Natl Cancer 2009; 101:1028). With the current study, we assessed how well uPA and PAI-1 values obtained from the core needle biopsy (in vivo) predict the expression level of these prognostic factors in the later surgical specimen. Material and Methods: Fresh frozen material of 2–3 core needle biopsies (min 10 mg each) and the corresponding tumor material (min 50 mg) removed by subsequent surgery were collected from 110 patients in two hospitals. Only areas of the surgical specimen were selected for testing that had a sufficient distance to the needle biopsy defect. The uPA and PAI-1 concentrations were analysed using a commercially available ELISA test (FEMTELLE™; American Diagnostica, Inc., Stamford, CT). The predictive values (and sensitivity/specificity) of the core-needle biopsy data were calculated to forecast the uPA and PAI-1 values of the corresponding surgical specimen results. Results: Sensitivity, specificity, the positive (ppv) and negative (npv) predictive values for uPA, PAI-1 and for the combination of uPA/PAI-1 are listed in table 1. Low concentrations of uPA in the core needle biopsies correlate with low concentrations in the surgical specimens across the entire study cohort as well as in the group with an intermediate (G2, N0) risk (npv = 0.91). The clinical and pathological data of the cohort and the risk assessment will be presented. Conclusion: Most important, low uPA/PAI-1 results in core-needle biopsies predict low results in the surgical specimen. In some cases, core-needle biopsies and surgical specimen show discordant data. These cases do not correlate with any clinical or pathological factors such as time between needling and surgery, grading, tumor size or hospital. We assume that these discordances are caused by pre-surgical manipulations, which change expression patterns in the remaining tissue as it is reported also from multi-gene tests. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-38.