Prognostic implications of securin expression and sub-cellular localization in human breast cancer

Abstract

Our data indicate that securin expression may serve as a strong and independent prognosticator of breast cancer outcome and that a cytoplasmic localization of the protein may provide additional prognostic information, particularly in the biologically and clinically challenging subgroup of triple-negative breast carcinomas. The sub-cellular localization of securin appears to reflect the expression of PTTG1IP, CDC20 and BUBR1, which may participate in the regulation of securin activity and, ultimately, in the survival of breast cancer patients.

PTTG1-interacting protein (PTTG1IP/PBF) predicts breast cancer survival

“…Securin IHC was performed with mouse monoclonal antibody (Abcam, ab3305, clone DCS-280, dilution 1:100) using Lab Vision Autostainer 480 (Thermo-Fisher Scientific, Fremont, CA, USA) and detection with PowerVision + polymer kit, according to standard protocol (DPVB + 110HRP; Immunovision Technologies, Vision Biosystems, Norwell, MA, USA). For oestrogen receptor (ER), progesterone receptor (PR), Ki-67 and HER2 IHC, an automated immunostaining BenchMark XT machine (Roche Diagnostics / Ventana) and an ultraView Universal DAB Detection Kit (Roche/Ventana) were used as described previously [ 9 , 12 ]. Initial HER2 testing was performed on basis of immunopositivity according to international guidelines and specimen representing 2+ and 3+ staining patterns were allocated for further verification [ 13 ].…”

“…LifeTechnologies, Eugene, OR, USA). More detailed description of the double staining has been published previously [ 9 ].…”

“…1 ). In each carcinoma case, the predominant subcellular localization of securin observed in >90% of cancer cells was registered as previously described [ 9 ].…”

“…This categorization was also supported by morphological observations of PTTG1IP immunohistochemistry in the breast cancer material and by the associated very high consistency of interpretations as calculated inter- and intraclass reproducibility. Categorization of securin immunoexpression was performed on the basis of the fraction of immunopositive cancer cells (<10% vs. ≥10%) and subcellular location (>90% of cancer cells showing cytoplasmic vs. nuclear expression) as described previously [ 9 , 12 ].…”

“…To our knowledge, no previous studies have evaluated PTTG1IP as a prognostic biomarker for breast carcinoma patients. We have previously presented that the lack of PTTG1IP in breast cancer cells is associated with cytoplasmic localization of securin and that this protein expression profile was overrepresented in the triple-negative breast cancers (TNBC) [ 9 ]. In the present paper, we report on the expression pattern of PTTG1IP in 497 breast carcinomas, with up to 22 years of follow-up.…”