Akt2 expression is associated with good long-term prognosis in oestrogen receptor positive breast cancer
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
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.
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.
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.
Breast cancer, Akt, Protein kinase B, Oestrogen receptor, Long-term, Prognostic factor
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-92610DOI: 10.1016/j.ejca.2012.12.006ISI: 000317188600005OAI: oai:DiVA.org:liu-92610DiVA: diva2:621697
Funding Agencies|Swedish Cancer Society||Swedish Research Council||2013-05-162013-05-142014-08-04