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

Abstract

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.

Crossroads: the role of biomarkers in the management of lumps in the breast

“…Most breast cancers produce the full-length form (OPN-a) together with the shortest splice variant (OPN-c). Remarkably, OPN-c is also present in a fraction of the premalignant lesions, where it reflects a high risk for progression to cancer within 5 years, regardless of the lesion's subtype [13,14]. With the simple immunohistochemical staining of the biopsied material, the individualized progression risk for that patient can be estimated with good sensitivity and specificity (Table 1), and it can lead to improved counseling.…”