title: Increased levels of SPARC (osteonectin) in human breast cancer tissues and its association with clinical outcomes.
abstract: SPARC (secreted protein acidic and rich in cystein), also known as osteonectin and BM40, is a 32 kDa secreted glycoprotein that interacts with extracellular matrix (ECM) proteins to promote adhesion of cells from the matrix, thereby inducing a biological state conducive to cell migration. SPARC is also thought to play an important role in tissue remodelling, angiogenesis, embryonic development and tumourigenesis. The current study set out to examine both the transcript levels of SPARC and the presence of the molecule in breast cancer tissue and to demonstrate if a link existed between the levels of SPARC and the clinical outcome. Breast tumour tissues (n=120) and non-neoplastic mammary tissues (n=32) were studied. Protein levels of SPARC were assessed using immunohistochemistry. Transcript levels of SPARC were analysed using RT-PCR. The levels were correlated with nodal status, grade, prognosis and long-term survival (10 years). Transcript levels of SPARC were found to be significantly higher in tumour tissue when compared to normal background breast tissue. This fact was mirrored when comparing levels of SPARC in ductal tumours with levels in lobular and other types of tumour. A high level of SPARC was also found in Grade 3 and TNM2 and TNM4 tumours. Node-positive tumours also exhibited higher levels of SPARC than node-negative tumours . It was also noted that SPARC was present in high levels in NPI 2 and NPI 3 tumours. Over a 6 year follow-up, high levels of SPARC was seen to be significantly associated with the overall survival of the patients (P=0.0198). However, there was no significant correlation with disease-free survival. It is concluded that SPARC plays a crucial role in tumour development in breast cancer and as such has a significant bearing on patient prognosis and long-term survival.
authors.affiliation: Metastasis & Angiogenesis Research Group, University Department of Surgery, Wales College of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Gareth
authors.initials: G
authors.lastname: Watkins
authors.forename: Anthony
authors.initials: A
authors.lastname: Douglas-Jones
authors.forename: Richard
authors.initials: R
authors.lastname: Bryce
authors.forename: Robert E
authors.initials: RE
authors.lastname: Mansel
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D014158:Transcription, Genetic / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D015676:Osteonectin; D012333:RNA, Messenger