title: Expression of proliferation genes in formalin-fixed paraffin-embedded (FFPE) tissue from breast carcinomas. Feasibility and relevance for a routine histopathology laboratory.
abstract: OBJECTIVE
  Breast carcinoma proliferative activity, histological grade and commercial molecular tests are all important in prognostication and treatment. There is a particular need for improved, standardised techniques for subclassification of grade 2 breast cancers into low-risk and high-risk prognostic groups. In this study we investigated whether gene expression profiling of five proliferation genes was feasible using breast cancer tissue in a clinical setting and whether these profiles could enhance pathological assessment.
  
  
  METHODS
  Expression of five proliferation gene mRNAs; Ki-67, STK 15, CCNB1, CCND1 and MYBL2, was quantified in 27 breast carcinomas and compared with Ki-67 proliferation index (PI) and Nottingham mitotic score.
  
  
  RESULTS
  Expression of Ki-67, STK15 and MYBL2 mRNA showed moderate Spearman's correlation with Ki-67 PI (p<0.01), but CCND1 and CCNB1 showed weak, non-significant correlation. Individual gene expression did not associate with mitotic score but combined mRNA expression correlated with both Ki-67 PI (p=0.018) and mitotic score (p=0.03; 0.007).
  
  
  CONCLUSIONS
  This study confirms mRNA analysis in breast carcinoma formalin-fixed, paraffin-embedded samples is feasible and suggests gene expression profiling, using a small set of five proliferation genes, has potential in aiding histological grading or assessment of proliferative activity of breast cancers. To fully evaluate the clinical applicability of this approach, a larger cohort study with long-term follow-up data is required.
authors.affiliation: Molecular Anatomical Pathology, PathWest, QEII Medical Centre, Nedlands, Western Australia, Australia.|School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Carla
authors.initials: C
authors.lastname: Thomas
authors.affiliation: Molecular Anatomical Pathology, PathWest, QEII Medical Centre, Nedlands, Western Australia, Australia.|School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia.|School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Cleo
authors.initials: C
authors.lastname: Robinson
authors.affiliation: Molecular Anatomical Pathology, PathWest, QEII Medical Centre, Nedlands, Western Australia, Australia.|School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Dessauvagie
authors.affiliation: Molecular Anatomical Pathology, PathWest, QEII Medical Centre, Nedlands, Western Australia, Australia.|School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wood
authors.affiliation: Molecular Anatomical Pathology, PathWest, QEII Medical Centre, Nedlands, Western Australia, Australia.|School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Greg
authors.initials: G
authors.lastname: Sterrett
authors.affiliation: Molecular Anatomical Pathology, PathWest, QEII Medical Centre, Nedlands, Western Australia, Australia.|School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Jennet
authors.initials: J
authors.lastname: Harvey
authors.affiliation: Molecular Anatomical Pathology, PathWest, QEII Medical Centre, Nedlands, Western Australia, Australia.|School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Benhur
authors.initials: B
authors.lastname: Amanuel
mesh_terms: D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D005557:Formaldehyde; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008940:Mitotic Index; D016612:Paraffin Embedding; D011379:Prognosis; D016707:Tissue Fixation / Q000379:methods; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C534699:CCNB1 protein, human; C530104:CCND1 protein, human; D018797:Cell Cycle Proteins; D056744:Cyclin B1; D019394:Ki-67 Antigen; C064352:MYBL2 protein, human; D015534:Trans-Activators; D019938:Cyclin D1; D005557:Formaldehyde; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: BREAST CANCER; KI 67; PROLIFERATION