29P - Effect of delays in time to fixation due to routine X-ray of surgical breast cancer specimens on gene expression profiles

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Breast Cancer
Translational Research
Presenter Elena Lopez Knowles
Citation Annals of Oncology (2015) 26 (suppl_3): 10-14. 10.1093/annonc/mdv116
Authors E.C. Lopez Knowles1, A. Gao1, F. Macneill2, I. Pinhel1, L.A. Martin1, M. Dowsett1
  • 1Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, london/UK
  • 2Breast Unit, Royal Marsden Hospital, london/UK



Background: Following surgical resection, breast cancer specimens are often X-rayed for evaluation of completion of resection. As a result a time delay occurs before fixation and/or collection of fresh tissue for study that may affect gene expression and its interpretation.

Aim: To evaluate the effect of the X-ray and time-elapsed on gene expression profiles in primary ER+ breast cancer.

Methods: 23 pairs of samples were taken from a surgical specimen immediately after resection and then after the routine X-ray: median time difference of 30 min (range 20-60min). All patients were postmenopausal ER+ receiving no neoadjuvant therapy. RNA was extracted from core cut biopsies stored in RNAlater and ran on the Illumina Whole Genome 47K array.

Results: A wound-healing signature (Chang HY et al, PNAS 2005), an inflammatory response metagene (Dunbier A et al, CCR 2013) and a 9 gene immune response list (Jesselsohn et al, PLOS ONE 2013) were compared between the paired samples and no statistically significant difference was observed. Overall changes in gene expression were minor but 68 genes were identified by Class Comparison as differentially expressed with p < 0.005 and fold change 1.25 (no probe changed with FDR <5%). These include early response, mitochondrial ATP synthase and stress response genes. The main canonical pathways were mitochondrial dysfunction, CDK5 and aldosterone signalling and the main networks were DNA repair and metabolic disease. 116 genes were identified whose expression change correlated with time elapsed (p < 0.005). The most significant canonical pathways were adipogenesis and mitochondrial dysfunction and the main networks were inflammation and metabolic disease. However, there were only 2 genes in common between the 68 and 116 gene list (SCD and AGPAT2).

Conclusion: There is a minimal impact of delay to fixation on gene expression profiles. Thus expression profiles from samples taken after treatment will be mainly due to the therapy and not the procedure associated with sample acquisition. However, some genes related to stress response may be affected and if observed should be considered as possibly related to sample procedure rather than treatment.

Disclosure: All authors have declared no conflicts of interest.