title: 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.
authors.affiliation: College of Pharmacy, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA.
authors.forename: Mana
authors.initials: M
authors.lastname: Mirza
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Shaughnessy
authors.forename: John K
authors.initials: JK
authors.lastname: Hurley
authors.forename: Kristie A
authors.initials: KA
authors.lastname: Vanpatten
authors.forename: Gary A
authors.initials: GA
authors.lastname: Pestano
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.forename: Georg F
authors.initials: GF
authors.lastname: Weber
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D020033:Protein Isoforms; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D053495:Osteopontin; D020033:Protein Isoforms; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen