Molecular Diagnostics

British Journal of Cancer (2005) 92, 120–124. doi:10.1038/sj.bjc.6602314 www.bjcancer.com
Published online 21 December 2004

Expression of survivin and its splice variants survivin-2B and survivin-DeltaEx3 in breast cancer

B Ryan1,4, N O'Donovan2,4, B Browne2, C O'Shea1, J Crown2, A D K Hill1, E McDermott1, N O'Higgins1,2 and M J Duffy1,3

  1. 1Department of Surgery, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland
  2. 2Department of Medical Oncology, St Vincent's University Hospital, Dublin 4, Ireland
  3. 3Department of Nuclear Medicine, St Vincent's University Hospital, Dublin 4, Ireland

Correspondence: Professor MJ Duffy, E-mail: Michael.J.Duffy@ucd.ie

4These authors contributed equally to this work

Received 30 June 2004; Revised 21 October 2004; Accepted 9 November 2004; Published online 21 December 2004.

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Abstract

Alternative splicing of survivin mRNA gives rise to multiple isoforms, that is, survivin and 3 splice variants, survivin-2B, survivin-3B and survivin-DeltaEx3. The aim of this study was to compare the expression of survivin, survivin-2B and survivin-DeltaEx3 in normal breast tissue, fibroadenomas, primary breast cancer and axillary nodal metastases. Survivin, survivin-2B and survivin-DeltaEx3 mRNA were measured using semiquantitative RT–PCR. In the primary carcinomas, we related mRNA for each form of survivin to both survivin protein and apoptosis. For each type of breast tissue, survivin was the predominant form detected, being present in 146 out of 156 (93.6%) primary breast carcinomas, 11 out of 11 (100%) axillary nodal metastases, 21 out of 31 (67.7%) fibroadenomas and five out of 22 (22.7%) specimens of normal breast tissue. Levels of the three forms of survivin were significantly higher in the carcinomas compared to normal breast tissue (P<0.0001). Levels of both survivin-2B and survivin-DeltaEx3 but not survivin were significantly higher in nodal metastases than primary carcinomas. Survivin mRNA levels correlated significantly with survivin protein. Finally, both survivin and survivin-DeltaEx3 but not survivin-2B correlated positively with apoptosis. Although survivin, survivin-2B and survivin-DeltaEx3 were all detected in both malignant and nonmalignant breast tissue, the predominant form was survivin. Our results suggest that the different forms of survivin may have different roles in apoptosis in breast cancer.

Keywords:

inhibitor of apoptosis, apoptosis, programmed cell death, breast carcinoma