Insitu hybridization for the assessment of urokinase plasminogen activator and plasminogen activator inhibitor type‑1 informalin‑fixed paraffin‑embedded breast cancer specimens.

Abstract

Urokinase plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor type1 (PAI‑1), have been reported as prognostic and predictive biomarkers in breast cancer, particularly in patients with node‑negative tumors. uPA and PAI‑1 expression levels classify patients into a poor‑prognosis subgroup, requiring adjuvant chemotherapy and a favorable‑prognosis subgroup, which can be considered for de‑escalation. However, the clinical use of these two biomarkers remains limited, since fresh‑frozen/fresh tumor samples are currently required for their quantification. The aim of the present study was to compare PLAU and SERPINE1 mRNA expression levels (corresponding to uPA and PAI‑1 proteins, respectively), assessed using insitu hybridization in 83 formalin‑fixed paraffin‑embedded (FFPE) breast tumor samples, with uPA and PAI‑1 protein expression assessed using immunometric assay with paired fresh‑frozen breast cancer samples. The results from the two methods significantly correlated as regards uPA quantification; however, >30% of the samples were discordant, according to the clinically validated threshold. Concordance between the two analytical methods was less prominent for PAI‑1 protein and SERPINE1 mRNA. Taken together, the results of the present study indicate that although PLAU and SERPINE1 mRNA may be reliably detected in FFPE samples using insitu hybridization, this technology cannot be used as a substitute for the replacement of the immunometric assay‑derived quantification on fresh‑frozen samples.