title: Loss of STARD10 expression identifies a group of poor prognosis breast cancers independent of HER2/Neu and triple negative status.
abstract: The phospholipid transfer protein STARD10 cooperates with c-erbB signaling and is overexpressed in Neu/ErbB2 breast cancers. We investigated if STARD10 expression provides additional prognostic information to HER2/neu status in primary breast cancer. A published gene expression dataset was used to determine relationships between STARD10 and HER2 mRNA levels and patient outcome. The central findings were independently validated by immunohistochemistry in a retrospective cohort of 222 patients with breast cancer with a median follow-up of 64 months. Kaplan-Meier and Cox proportional hazards analyses were used for univariate and multivariate analyses. Patients with low STARD10 or high HER2 tumor mRNA levels formed discrete groups each associated with a poor disease-specific survival (p = 0.0001 and p = 0.0058, respectively). In the immunohistochemical study low/absent STARD10 expression i.e. < or = 10% positive cells was observed in 24 of 222 (11%) tumors. In a univariate model, low/absent STARD10 expression was significantly associated with decreased patient survival (p = 0.0008). In multivariate analyses incorporating tumor size, tumor grade, lymph node status, ER, PR and HER2 status, low STARD10 expression was an independent predictor of death from breast cancer (HR: 2.56 (95% CI: 1.27-5.18), p = 0.0086). Furthermore, low/absent STARD10 expression, HER2 amplification and triple negative status were independent prognostic variables. Loss of STARD10 expression may provide an additional marker of poor outcome in breast cancer identifying a subgroup of patients with a particularly adverse prognosis, which is independent of HER2 amplification and the triple negative phenotype.
authors.affiliation: Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.
authors.forename: Niamh C
authors.initials: NC
authors.lastname: Murphy
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Biankin
authors.forename: Ewan K A
authors.initials: EK
authors.lastname: Millar
authors.forename: Catriona M
authors.initials: CM
authors.lastname: McNeil
authors.forename: Sandra A
authors.initials: SA
authors.lastname: O'Toole
authors.forename: Davendra
authors.initials: D
authors.lastname: Segara
authors.forename: Paul
authors.initials: P
authors.lastname: Crea
authors.forename: Monilola A
authors.initials: MA
authors.lastname: Olayioye
authors.forename: C Soon
authors.initials: CS
authors.lastname: Lee
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Fox
authors.forename: Adrienne L
authors.initials: AL
authors.lastname: Morey
authors.forename: Michael
authors.initials: M
authors.lastname: Christie
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Musgrove
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Daly
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Lindeman
authors.forename: Susan M
authors.initials: SM
authors.lastname: Henshall
authors.forename: Jane E
authors.initials: JE
authors.lastname: Visvader
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sutherland
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D015999:Multivariate Analysis; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D010750:Phosphoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C488090:STARD10 protein, human