Differentiating borderline HER2-expressing and HER2-positive cancers from other subtypes using serum urokinase plasminogen activator.

BACKGROUND

HER2-positive (HER2+) cancers are associated with aggressive tumour development but also high response rates to targeted blockade treatments of the HER-2/neu signalling pathway leading to improved clinical outcome for the patient. Current clinical analysis of the HER2 status primarily relies on solid tumour 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 tumour-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 precisely stratifies patients with HER-2/neu overexpressing (HER2+) and borderline-expressing cancers. Serum levels of total uPA 96.8% accurately informed about HER-2/neu tumour status in a cohort of 100 patients, with a HER2+/borderline expression cut-off value of 0.973 ng mL-1.

CONCLUSIONS

The established liquid biopsy test for serum uPA has potential for accurate diagnosis and staging of patients with HER2+ and borderline-expressing cancers requiring further confirmatory (or rejection) testing.