Breast cancer risk in papilloma patients: Osteopontin splice variants indicate prognosis

BACKGROUND: Papillomas of the breast pose challenges for treatment decisions as their risk for transformation to breast cancer is low but not negligible. To spare low-risk patients the burden of substantial treatment side effects, prognostic indicators are needed for cancerous progression. The secreted metastasis mediator Osteopontin (OPN) is a marker for breast cancer aggressiveness, and its variants are prognosticators for transformation in diverse premalignant breast lesions. Here, we test whether the presence of OPN-c or OPN-exon-4 in papillomatous lesions may reflect progression risk. METHODS: By immunohistochemistry, we analyze OPN-c and OPN-exon-4 in papillomas from 114 women as well as correlations between staining and progression. In departure from prior spliced OPN biomarker publications, we utilize novel monoclonal antibodies. RESULTS: Fewer than 5% of OPN-c pathology score 0–1 (intensity) versus almost 18% of score 2–3 experienced cancer in follow-up. Nine of 12 women, who progressed, had pathology scores of 2–3 for OPN-c intensity at the time of initial diagnosis, and none had a score of 0. When developing a combined risk score from intensity plus percent positivity for OPN-c, the progression risk for patients with low score was 3.2%, for intermediate score was 5.7%, and for high score was 18.8%. Papillomas in patients, who were later diagnosed with cancer in the contralateral breast, displayed stronger staining positivity than non-progressors. CONCLUSION: OPN splice variant immunohistochemistry on biopsies of breast papillomas will allow counseling of the patients on their risk to develop breast cancer at a later time. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-022-01561-9.