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Akt2 expression is associated with good long-term prognosis in oestrogen receptor positive breast cancer
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
Karolinska University Hospital, Sweden.
Karolinska University Hospital, Sweden.
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2013 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, no 6, 1196-1204 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier , 2013. Vol. 49, no 6, 1196-1204 p.
Keyword [en]
Breast cancer, Akt, Protein kinase B, Oestrogen receptor, Long-term, Prognostic factor
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-92610DOI: 10.1016/j.ejca.2012.12.006ISI: 000317188600005OAI: oai:DiVA.org:liu-92610DiVA: diva2:621697
Note

Funding Agencies|Swedish Cancer Society||Swedish Research Council||

Available from: 2013-05-16 Created: 2013-05-14 Last updated: 2017-12-06

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Fohlin, HelenaPerez-Tenorio, GizehNordenskjöld, BoCarstensen, JohnStål, Olle
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