Osteopontin‐c is a selective marker of breast cancer

Abstract

While the acquisition of invasiveness is a critical step in early stage breast carcinomas (DCIS), no established molecular markers reliably identify tumor progression. The metastasis gene osteopontin is subject to alternative splicing, which yields 3 messages, osteopontin‐a, osteopontin‐b and osteopontin‐c. Osteopontin‐c is selectively expressed in invasive, but not in noninvasive, breast tumor cell lines, and it effectively supports anchorage independence. We evaluated osteopontin‐c as a biomarker. The RNA message for osteopontin‐c was present in 16 of 20 breast cancers (80%), but was undetectable in 22 normal specimens obtained from reduction mammoplasty. In contrast, osteopontin‐a RNA was expressed at various levels in all 20 breast cancers, 11 tumor‐surrounding tissues and 21 normal samples. The splice variant osteopontin‐b was present at barely detectable levels in 18 of 20 cancers and in 6 of 22 normal breasts. By immunohistochemistry, 66 of 69 normal breasts were negative, while 3 showed low level staining. Among the breast cancers, 43 of 56 cores (77%) stained positive for osteopontin‐c. When correlated with tumor grade, the staining for osteopontin‐c increased from grade 1 to grade 3. In a total of 178 breast specimens analyzed, osteopontin‐c was present in 78% of cancers, 36% of surrounding tissues and 0% of normal tissues. Furthermore, osteopontin‐c detects a higher fraction of breast cancers than estrogen receptor (ER), progesterone receptor or HER2. In conjunction, osteopontin‐c, ER and HER2 reliably predict grade 2–3 breast cancer. Hence, osteopontin‐c is a diagnostic and prognostic marker that may have value in a diagnostic panel together with conventional breast cancer markers.