Nuclear osteopontin-c is a prognostic breast cancer marker

The goals of cancer therapy are to eliminate the transformed cells, limit the risk of local recurrence and minimise the prospect of invasive spread. In breast cancer, it is based on surgery (lumpectomy or mastectomy) and adjuvant treatment (hormonal therapy, chemotherapy and radiation). Treatment choices are difficult to make for individual patients, because there are no predictors for their specific progression risk. While an early diagnosis is critical for the successful management of the disease, the detection of early-stage lesions poses the challenge of accurately assessing the risk of breast cancer recurrence and death. Available diagnostic techniques involve a biopsy where samples of tissue are taken to confirm or eliminate the presence of cancer cells by histopathological examination. While this procedure is a standard at present, it does not detect invasive potential. The prognostic/predictive factors most commonly used to select patients for adjuvant therapy are age, lymph node status, tumor size, hormone receptors, histologic grade, proliferation (Ki-67) and human epidermal growth factor receptor 2 (HER2). The oestrogen receptor status is used for prediction of endocrine responsiveness, Ki-67 to assess the likelihood of response to chemotherapy and HER2 status to determine the need of HER2-directed therapy. The practiced regimen can be improved if reliable molecular markers are identified to assess the aggressiveness of a tumor at an early stage. By including such an evaluation, physicians will be better able to determine appropriate treatment options for their patients. Osteopontin has been associated with the progression of numerous types of cancer (Weber et al, 2010, 2011; Weber, 2011), including those of the breast. The full-length form of the molecule (Osteopontin-a) physiologically acts as a TH1 cytokine that may be secreted by macrophages and T-lymphocytes and is elevated in the blood during immune responses (Ashkar et al, 2000). Further, the osteopontin gene (SPP1) is oestrogen responsive (Craig and Denhardt, 1991) and Osteopontin-a is secreted during lactation (Senger et al, 1989), limiting its value as a breast cancer marker. We have identified the splice variant Osteopontin-c (He et al, 2006) to be selectively present in specific cancers including those of the breast (Mirza et al, 2008; Sullivan et al, 2009; Tilli et al, 2011), but not in healthy tissue, and to serve as a marker for tumor grade (Mirza et al, 2008; Hartung and Weber, 2013). These studies were done by immunohistochemistry or by real-time RT–PCR on the cancer tissues or in patient blood. A prognostic role for Osteopontin-c RNA in breast cancer has been suggested independently (Patani et al, 2008a, 2008b). Here, we study the value of Osteopontin-c immunohistochemistry as a prognostic indicator in breast cancer.