title: Ki67/SATB1 ratio is an independent prognostic factor of overall survival in patients with early hormone receptor-positive invasive ductal breast carcinoma.
abstract: Biological diversity of breast cancer presents challenges for personalized therapy and necessitates multiparametric approaches to understand and manage the disease. Multiple protein biomarkers tested by immunohistochemistry (IHC), followed by digital image analysis and multivariate statistics of the data, have been shown to be effective in exploring latent profiles of tumor tissue immunophenotype. In this study, based on tissue microarrays of 107 patients with hormone receptor (HR) positive invasive ductal breast carcinoma, we investigated the prognostic value of the integrated immunophenotype to predict overall survival (OS) of the patients. A set of 10 IHC markers (ER, PR, HER2, Ki67, AR, BCL2, HIF-1α, SATB1, p53, and p16) was used. The main factor of the variance was characterized by opposite loadings of ER/PR/AR/BCL2 and Ki67/HIF-1α; it was associated with histological grade but did not predict OS. The second factor was driven by SATB1 expression along with moderate positive HIF-1α and weak negative Ki67 loadings. Importantly, this factor did not correlate with any clinicopathologic parameters, but was an independent predictor of better OS. Ki67 and SATB1 did not reach statistical significance as single predictors; however, high Ki67/SATB1 ratio was an independent predictor of worse OS. In addition, our data indicate potential double prognostic meaning of HIF-1α expression in breast cancer and necessitate focused studies, taking into account the immunophenotype interactions and tissue heterogeneity aspects.
authors.affiliation: Faculty of Medicine, Vilnius University, Vilnius, Lithuania.|National Center of Pathology, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania.
authors.forename: Arvydas
authors.initials: A
authors.lastname: Laurinavicius
authors.affiliation: Division of Cancer and Stem Cells, School of Medicine and Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Green
authors.affiliation: Faculty of Medicine, Vilnius University, Vilnius, Lithuania.|National Center of Pathology, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania.
authors.forename: Aida
authors.initials: A
authors.lastname: Laurinaviciene
authors.affiliation: Faculty of Medicine, Vilnius University, Vilnius, Lithuania.|National Cancer Institute, Vilnius, Lithuania.
authors.forename: Giedre
authors.initials: G
authors.lastname: Smailyte
authors.affiliation: National Cancer Institute, Vilnius, Lithuania.
authors.forename: Valerijus
authors.initials: V
authors.lastname: Ostapenko
authors.affiliation: National Center of Pathology, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania.
authors.forename: Raimundas
authors.initials: R
authors.lastname: Meskauskas
authors.affiliation: Division of Cancer and Stem Cells, School of Medicine and Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000532:radiotherapy; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000378:metabolism* / Q000532:radiotherapy; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism*; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011987:Receptors, Steroid / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019394:Ki-67 Antigen; D036961:Matrix Attachment Region Binding Proteins; D011987:Receptors, Steroid; C076189:SATB1 protein, human
keywords: HIF-1α; SATB1; breast cancer; digital image analysis; immunohistochemistry