Expression of proliferation genes in formalin-fixed paraffin-embedded (FFPE) tissue from breast carcinomas. Feasibility and relevance for a routine histopathology laboratory

J Clin Pathol. 2017 Jan;70(1):25-32. doi: 10.1136/jclinpath-2016-203786. Epub 2016 May 27.

Abstract

Aim: 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.

Keywords: BREAST CANCER; KI 67; PROLIFERATION.

MeSH terms

  • Aurora Kinase A / genetics
  • Aurora Kinase A / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cyclin B1 / genetics
  • Cyclin B1 / metabolism
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Feasibility Studies
  • Female
  • Formaldehyde
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Mitotic Index
  • Paraffin Embedding
  • Prognosis
  • Tissue Fixation / methods
  • Trans-Activators / genetics
  • Trans-Activators / metabolism

Substances

  • Biomarkers, Tumor
  • CCNB1 protein, human
  • CCND1 protein, human
  • Cell Cycle Proteins
  • Cyclin B1
  • Ki-67 Antigen
  • MYBL2 protein, human
  • Trans-Activators
  • Cyclin D1
  • Formaldehyde
  • AURKA protein, human
  • Aurora Kinase A