title: Akt2 expression is associated with good long-term prognosis in oestrogen receptor positive breast cancer.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Regional Cancer Center, Southeast Sweden, County Council of Östergötland, Linköping, Sweden. helena.fohlin@lio.se
authors.forename: Helena
authors.initials: H
authors.lastname: Fohlin
authors.forename: Gizeh
authors.initials: G
authors.lastname: Pérez-Tenorio
authors.forename: Tommy
authors.initials: T
authors.lastname: Fornander
authors.forename: Lambert
authors.initials: L
authors.lastname: Skoog
authors.forename: Bo
authors.initials: B
authors.lastname: Nordenskjöld
authors.forename: John
authors.initials: J
authors.lastname: Carstensen
authors.forename: Olle
authors.initials: O
authors.lastname: Stål
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D059248:Chemoradiotherapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000378:metabolism*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D011960:Receptors, Estrogen; C494918:AKT1 protein, human; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt