title: Protein kinase CK2α subunit over-expression correlates with metastatic risk in breast carcinomas: quantitative immunohistochemistry in tissue microarrays.
abstract: BACKGROUND
  CK2α is a signalling molecule that participates in major events in solid tumour progression. The aim of this study was to evaluate the prognostic significance of the immunohistochemical expression of CK2α in breast carcinomas.
  
  
  METHODS
  Quantitative measurements of immunohistochemical expression of 33 biomarkers using high-throughput densitometry, assessed on digitised microscopic tissue micro-array images were correlated with clinical outcome in 1000 breast carcinomas using univariate and multivariate analyses.
  
  
  RESULTS
  In univariate analysis, CK2α was a significant prognostic indicator (p<0.001). Moreover, a multivariable model allowed the selection of the best combination of the 33 biomarkers to predict patients' outcome through logistic regression. A nine-marker signature highly predictive of metastatic risk, associating SHARP-2, STAT1, eIF4E, pmapKAPk-2, pAKT, caveolin, VEGF, FGF-1 and CK2α permitted to classify well 82.32% of patients (specificity 81.59%, sensitivity 92.55%, area under ROC curve 0.939). Importantly, in a node negative subset of patients an even more (86%) clinically relevant association of eleven markers was found predictive of poor outcome.
  
  
  CONCLUSIONS
  A strong quantitative CK2α immunohistochemical expression in breast carcinomas is individually a significant indicator of poor prognosis. Moreover, an immunohistochemical signature of 11 markers including CK2α accurately (86%) well classifies node negative patients in good and poor outcome subsets. Our results suggest that CK2α evaluation together with key downstream CK2 targets might be a useful tool to identify patients at high risk of distant metastases and that CK2 can be considered as a relevant target for potential specific therapy.
authors.affiliation: Department of Pathology, Hôpital Nord and Université de la Méditerranée, 13915 Marseille cedex 20, France. sophie.giusiano@ap-hm.fr
authors.forename: Sophie
authors.initials: S
authors.lastname: Giusiano
authors.forename: Claude
authors.initials: C
authors.lastname: Cochet
authors.forename: Odile
authors.initials: O
authors.lastname: Filhol
authors.forename: Eve
authors.initials: E
authors.lastname: Duchemin-Pelletier
authors.forename: Véronique
authors.initials: V
authors.lastname: Secq
authors.forename: Pascal
authors.initials: P
authors.lastname: Bonnier
authors.forename: Xavier
authors.initials: X
authors.lastname: Carcopino
authors.forename: Léon
authors.initials: L
authors.lastname: Boubli
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: Stéphane
authors.initials: S
authors.lastname: Garcia
authors.forename: Juan
authors.initials: J
authors.lastname: Iovanna
authors.forename: Colette
authors.initials: C
authors.lastname: Charpin
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis*; D047390:Casein Kinase II / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009362:Neoplasm Metastasis; D011379:Prognosis; D012372:ROC Curve; D012307:Risk Factors; D046888:Tissue Array Analysis / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D047390:Casein Kinase II