Loss of STARD10 expression identifies a group of poor prognosis breast cancers independent of HER2/Neu and triple negative status

Niamh C Murphy, Andrew V Biankin, Ewan K Millar, Catriona M McNeil, Sandra A O'Toole, Davendra Segara, Paul Crea, Monilola Olayioye, C Soon Lee, Stephen B Fox, Adrienne Morey, Michael Christie, Elizabeth A Musgrove, Roger John Daly, Geoffrey J Lindeman, Susan M Henshall, Jane Visvader, Robert L Sutherland

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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.
Original languageEnglish
Pages (from-to)1445 - 1453
Number of pages9
JournalInternational Journal of Cancer
Issue number6
Publication statusPublished - 2010
Externally publishedYes

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