title: Overexpression of the oncogenic signal transducer Gab2 occurs early in breast cancer development.
abstract: Gab2, a docking-type signaling protein with demonstrated oncogenic potential, is overexpressed in breast cancer, but its prognostic significance and role in disease evolution remain unclear. Immunohistochemical detection of Gab2 in a large cohort of primary human breast cancers of known outcome revealed that while Gab2 expression was positively correlated with increased tumor grade, it did not correlate with disease recurrence or breast cancer-related death in the total cohort or in patients stratified according to lymph node, estrogen receptor (ER) or HER2 status. Interestingly, analysis of a "progression series" that included premalignant and preinvasive breast lesions as well as samples of metastatic disease revealed that Gab2 expression was significantly enhanced in the earliest lesion examined, usual ductal hyperplasia, with a further increase detected in ductal carcinoma in situ (DCIS). Furthermore, expression was less in invasive cancers and lymph node metastases than in DCIS, but still higher than in normal breast. These findings indicate that while Gab2 expression is not prognostic in breast cancer, its role in early disease evolution warrants further analysis, as Gab2 and its effectors may provide targets for novel strategies aimed at preventing breast cancer development.
authors.affiliation: Cancer Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
authors.forename: Emmy D G
authors.initials: ED
authors.lastname: Fleuren
authors.forename: Sandra
authors.initials: S
authors.lastname: O'Toole
authors.forename: Ewan K
authors.initials: EK
authors.lastname: Millar
authors.forename: Catriona
authors.initials: C
authors.lastname: McNeil
authors.forename: Elena
authors.initials: E
authors.lastname: Lopez-Knowles
authors.forename: Alice
authors.initials: A
authors.lastname: Boulghourjian
authors.forename: David R
authors.initials: DR
authors.lastname: Croucher
authors.forename: Daniel
authors.initials: D
authors.lastname: Schramek
authors.forename: Tilman
authors.initials: T
authors.lastname: Brummer
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sutherland
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Daly
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490895:GAB2 protein, human; D011960:Receptors, Estrogen