Akt2 expression is associated with good long-term prognosis in oestrogen receptor positive breast cancer.

Abstract

INTRODUCTION:

Akt is a signalling modulator for many cellular processes, including metabolism, cell proliferation, cell survival and cell growth. Three isoforms of Akt have been identified, but only a few studies have concerned the isoform-specific roles in the prognosis of breast cancer patients. The aim of this study was to investigate the prognostic value of v-akt murine thymoma viral oncogene homologue 1 (Akt1) and v-akt murine thymoma viral oncogene homologue 2 (Akt2) in oestrogen receptor positive (ER+) and oestrogen receptor negative (ER-) breast cancer with long-term follow-up.

MATERIAL AND METHODS:

The expression of Akt in tumour tissue was analysed with immunohistochemistry in a cohort of 272 postmenopausal patients with stage II breast cancer. The median follow-up time was 19 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox's proportional hazards model.

RESULTS:

The risk of distant recurrence was reduced for patients with ER+ tumours expressing Akt2 compared to patients with no Akt2 expression (HR=0.49, 95% CI 0.29-0.82, p=0.007). When adjusting for important clinical tumour characteristics and treatment, Akt2 was still an independent prognostic factor (HR=0.38, 95% CI 0.21-0.68, p=0.001) and the association remained long-term. The prognostic value of Akt2 increased with higher oestrogen receptor levels from no effect among patients with ER- tumours to 68% risk reduction for the group with high ER-levels (P for trend=0.042). Akt1 showed no significant prognostic information.

CONCLUSION:

Our results indicate that Akt2 expression is associated with a lower distant recurrence rate for patients with ER+ tumours and that this association remains long-term. The prognostic value of Akt2 increases with higher oestrogen receptor expression, motivating further mechanistic studies on the role of Akt2 in ER+ breast cancer.

• Authors: Helena Fohlin, Gizeh Pérez-Tenorio, Tommy Fornander, Lambert Skoog, Bo Nordenskjöld, John Carstensen, Olle Stål
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 49 Issue 6 Pg. 1196-204 (Apr 2013) ISSN: 1879-0852 [Electronic] England
• PMID: 23305873 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Receptors, Estrogen
• AKT1 protein, human
• AKT2 protein, human
• Proto-Oncogene Proteins c-akt

Topics

• Adult
• Aged
• Breast Neoplasms (diagnosis, metabolism, therapy)
• Chemoradiotherapy
• Female
• Follow-Up Studies
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Middle Aged
• Multivariate Analysis
• Prognosis
• Proto-Oncogene Proteins c-akt (biosynthesis)
• Receptors, Estrogen (metabolism)
• Time Factors
• Treatment Outcome