Differentiating Borderline HER2 -Expressing and HER2 -Positive Cancers from Other Subtypes Using Serum Urokinase Plasminogen Activator

Abstract Background HER2 -positive ( HER2 +) cancers are associated with aggressive tumor development but also high response rates to targeted blockade treatments of the HER-2/ neu signaling pathway leading to improved clinical outcome for the patient. Current clinical analysis of the HER2 status primarily relies on solid tumor biopsies low-suitable for continuous real-time monitoring needed for possible adjustment of the treatment, while serum tests targeting blood-circulating HER-2/ neu fragments often show conflicting tumor-serum relations. Methods A cellulase-linked aptamer sandwich assay was used for detection of total urokinase plasminogen activator (uPA) and its different forms in serum of cancer patients and healthy individuals. Serum uPA levels were correlated with solid biopsy results and relevant clinical data extracted from electronic patient records, and FDG-PET/CT scanning. Results We show that serum uPA allows precise stratification of patients with HER2 + cancers and cancers with HER2 borderline expression. Serum levels of total uPA 96.6% accurately informed about HER2 + tumor status in a cohort of 85 patients, with a HER2 + cut-off value of 0.976 ng mL -1 . Conclusions The established liquid biopsy test for serum uPA has potential for accurate diagnosis and staging of patients with HER2 + cancers and “borderline” cancers requiring further confirmatory (or rejection) testing.