PubMed:15642160 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/15642160","sourcedb":"PubMed","sourceid":"15642160","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/15642160","text":"Immunohistochemical expression of insulin-like growth factor binding protein-3 in invasive breast cancers and ductal carcinoma in situ: implications for clinicopathology and patient outcome.\nINTRODUCTION: Insulin-like growth factor binding protein-3 (IGFBP-3) differentially modulates breast epithelial cell growth through insulin-like growth factor (IGF)-dependent and IGF-independent pathways and is a direct (IGF-independent) growth inhibitor as well as a mitogen that potentiates EGF (epidermal growth factor) and interacts with HER-2. Previously, high IGFBP-3 levels in breast cancers have been determined by enzyme-linked immunosorbent assay and immunoradiometric assay methods. In vitro, IGFBP-3's mechanisms of action may involve cell membrane binding and nuclear translocation. To evaluate tumour-specific IGFBP-3 expression and its subcellular localisation, this study examined immunohistochemical IGFBP-3 expression in a series of invasive ductal breast cancers (IDCs) with synchronous ductal carcinomas in situ (DCIS) in relation to clinicopathological variables and patient outcome.\nMETHODS: Immunohistochemical expression of IGFBP-3 was evaluated with the sheep polyclonal antiserum (developed in house) with staining performed as described previously.\nRESULTS: IGFBP-3 was evaluable in 101 patients with a variable pattern of cytoplasmic expression (positivity of 1+/2+ score) in 85% of invasive and 90% of DCIS components. Strong (2+) IGFBP-3 expression was evident in 32 IDCs and 40 cases of DCIS. A minority of invasive tumours (15%) and DCIS (10%) lacked IGFBP-3 expression. Nuclear IGFBP-3 expression was not detectable in either invasive cancers or DCIS, with a consistent similarity in IGFBP-3 immunoreactivity in IDCs and DCIS. Positive IGFBP-3 expression showed a possible trend in association with increased proliferation (P = 0.096), oestrogen receptor (ER) negativity (P = 0.06) and HER-2 overexpression (P = 0.065) in invasive tumours and a strong association with ER negativity (P = 0.037) in DCIS. Although IGFBP-3 expression was not an independent prognosticator, IGFBP-3-positive breast cancers may have shorter disease-free and overall survivals, although these did not reach statistical significance.\nCONCLUSIONS: Increased breast epithelial IGFBP-3 expression is a feature of tumorigenesis with cytoplasmic immunoreactivity in the absence of significant nuclear localisation in IDCs and DCIS. There are trends between high levels of IGFBP-3 and poor prognostic features, suggesting that IGFBP-3 is a potential mitogen. IGFBP-3 is not an independent prognosticator for overall survival or disease-free survival, to reflect its dual effects on breast cancer growth regulated by complex pathways in vivo that may relate to its interactions with other growth factors.","tracks":[{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":2276,"end":2283},"obj":"gene:3486"},{"id":"T1","span":{"begin":2311,"end":2324},"obj":"disease:C0596263"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"15642160-0#34#78#gene3486","span":{"begin":34,"end":78},"obj":"gene3486"},{"id":"15642160-0#91#105#diseaseC0006142","span":{"begin":91,"end":105},"obj":"diseaseC0006142"},{"id":"15642160-0#110#134#diseaseC0007124","span":{"begin":110,"end":134},"obj":"diseaseC0007124"},{"id":"15642160-12#28#35#gene3486","span":{"begin":2276,"end":2283},"obj":"gene3486"},{"id":"15642160-12#63#76#diseaseC0596263","span":{"begin":2311,"end":2324},"obj":"diseaseC0596263"},{"id":"15642160-14#0#7#gene3486","span":{"begin":2554,"end":2561},"obj":"gene3486"},{"id":"15642160-14#123#136#diseaseC0678222","span":{"begin":2677,"end":2690},"obj":"diseaseC0678222"},{"id":"15642160-4#28#35#gene3486","span":{"begin":815,"end":822},"obj":"gene3486"},{"id":"15642160-4#121#128#gene3486","span":{"begin":908,"end":915},"obj":"gene3486"},{"id":"15642160-4#210#227#diseaseC1176475","span":{"begin":997,"end":1014},"obj":"diseaseC1176475"}],"relations":[{"id":"34#78#gene348691#105#diseaseC0006142","pred":"associated_with","subj":"15642160-0#34#78#gene3486","obj":"15642160-0#91#105#diseaseC0006142"},{"id":"34#78#gene3486110#134#diseaseC0007124","pred":"associated_with","subj":"15642160-0#34#78#gene3486","obj":"15642160-0#110#134#diseaseC0007124"},{"id":"28#35#gene348663#76#diseaseC0596263","pred":"associated_with","subj":"15642160-12#28#35#gene3486","obj":"15642160-12#63#76#diseaseC0596263"},{"id":"0#7#gene3486123#136#diseaseC0678222","pred":"associated_with","subj":"15642160-14#0#7#gene3486","obj":"15642160-14#123#136#diseaseC0678222"},{"id":"28#35#gene3486210#227#diseaseC1176475","pred":"associated_with","subj":"15642160-4#28#35#gene3486","obj":"15642160-4#210#227#diseaseC1176475"},{"id":"121#128#gene3486210#227#diseaseC1176475","pred":"associated_with","subj":"15642160-4#121#128#gene3486","obj":"15642160-4#210#227#diseaseC1176475"}],"attributes":[{"subj":"15642160-0#34#78#gene3486","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15642160-0#91#105#diseaseC0006142","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15642160-0#110#134#diseaseC0007124","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15642160-12#28#35#gene3486","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15642160-12#63#76#diseaseC0596263","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15642160-14#0#7#gene3486","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15642160-14#123#136#diseaseC0678222","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15642160-4#28#35#gene3486","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15642160-4#121#128#gene3486","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15642160-4#210#227#diseaseC1176475","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"PubMed_Structured_Abstracts","denotations":[{"id":"T1","span":{"begin":205,"end":1095},"obj":"BACKGROUND"},{"id":"T2","span":{"begin":1105,"end":1266},"obj":"METHODS"},{"id":"T3","span":{"begin":1276,"end":2234},"obj":"RESULTS"},{"id":"T4","span":{"begin":2248,"end":2798},"obj":"CONCLUSIONS"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T2","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T3","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T4","pred":"source","obj":"PubMed_Structured_Abstracts"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"DisGeNET","color":"#ecbe93","default":true},{"id":"DisGeNET5_gene_disease","color":"#a493ec"},{"id":"PubMed_Structured_Abstracts","color":"#9bec93"}]}]}}