Increased expression of osteopontin in patients with triple-negative breast cancer

Abstract

Background: Patients with triple-negative [oestrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER-2/neu) negative] breast cancer, accounting for about 15% of breast cancer cases, are associated with aggressive histology, poor prognosis and shorter survival. Osteopontin is a chemokine-like phosphorylated glycoprotein that plays important role in cancer progression and is found to be a metastasis-associated protein in breast cancer. The goal of the study was to evaluate osteopontin protein expression levels in triple-negative breast carcinomas to determine if they correlated with clinicopathological parameters, thus providing additional support for osteopontin functioning and better understanding of triple-negative breast cancer.

Materials and methods: A database of 239 patients, in whom all three markers (ER, PR, and HER-2/neu) were available, was reviewed. We performed osteopontin protein expression analyses by means of immunohistochemistry on 117 breast carcinoma tissue samples, and then assessed the mean value of osteopontin expression against triple-negative status and clinicopathological parameters.

Results: Of the 239 patients in the study, 47 were classified as triple negative. Of the 117 osteopontin-test patients in this cohort, mean osteopontin levels were significantly higher in the triple-negative breast cancers than in non-triple-negative subtype (P = 0.035). TNM (tumours, nodes, metastases) stage were significantly associated with osteopontin levels (P = 0.038). Univariate analysis showed tumour cell osteopontin positivity above an optimized cut-point to be significantly associated with decreased disease-free survival, but not overall survival. In the multivariate model, osteopontin was an independent prognostic factor for disease-free survival.

Conclusions: Patients with osteopontin overexpression develop predominantly triple-negative tumours. Osteopontin overexpression is associated with tumour aggressiveness and poor prognosis.