Loss of STARD 10 expression identifies a group of poor prognosis breast cancers independent of HER2/Neu and triple negative status

Murphy, NC; Biankin, AV; Millar, EKA; McNeil, CM; O&#39;Toole, SA; Segara, D; Crea, P; Olayioye, MA; Lee, CS; Fox, SB; Morey, AL; Christie, M; Musgrove, EA; Daly, RJ; Lindeman, GJ; Henshall, SM; Visvader, JE; Sutherland, RL

Author(s): Murphy, NC; Biankin, AV; Millar, EKA; McNeil, CM; O'Toole, SA; Segara, D; Crea, P; Olayioye, MA; Lee, CS; Fox, SB; Morey, AL; Christie, M; Musgrove, EA; Daly, RJ; Lindeman, GJ; Henshall, SM; Visvader, JE; Sutherland, RL;
Details: Publication Year 2010-03-15,Volume 126,Issue #6,Page 1445-1453
Journal Title: INTERNATIONAL JOURNAL OF CANCER
Publication Type: Journal Article
Abstract: The phospholipid transfer protein STARD10 cooperates with c-er6B signaling and is overexpressed in Neu/Er682 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. <= 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.
Publisher: JOHN WILEY & SONS INC
Keywords: RANDOMIZED-TRIALS; AMERICAN-SOCIETY; RESPONSIVE GENES; TRANSFER PROTEIN; TAMOXIFEN; THERAPY; RECOMMENDATIONS; OVEREXPRESSION; TUMORIGENESIS; C-ERBB2
Publisher's Version: https://doi.org/10.1002/ijc.24826
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2010-03-15 12:00:00