AKT-1 and BCL-2 co-expression in breast cancer patients correlates with better survival

Background and purpose

Akt-1 is a serine/threonine-protein kinase that regulates growth factor-dependent cell proliferation and survival. Activated-Akt-1 causes Bcl-2 release from the BAD:Bcl-2 inactive complex. Bcl-2 is not only able to prevent apoptosis, as a downstream effector of Akt-1, but also can delay cell-cycle progression. Akt-1 is over-expressed in breast cancer cell lines and tumours, while Bcl-2 has been related with tumour survival and drug resistance in vitro and to an ER+/well differentiated sub-group of tumours, in vivo. Since endocrine treatment effectiveness could be due to activation of the apoptotic program, we wanted to investigate the expression and relationship between these factors as well as other variables (C-erbB-2, ER, and S-phase).

Patients and methods

Frozen tissue from primary tumours of 104 breast cancer patients (age <50 years), who received tamoxifen, zoladex or both (follow-up period >10 years), was used to determine the expression of Bcl-2 and Akt-1 by immunohistochemistry. C-erbB-2 expression and S-phase were analysed using flow cytometry. The statistical analysis was performed using the 'Statistica' package.

Results

There was a positive correlation between Bcl-2 and Akt-1 expression (38 Akt-1+/65 Bcl-2+ compared with 11 Akt-1+/37 Bcl-2- cases, P = 0.007). This correlation also appears in metastasis-free patients (P = 0.0008) but not in those patients with metastasis (P = 1.0). Bcl-2 alone was not significantly associated with ER, S-phase or c-erbB-2 expression (P > 0.05) but a trend was observed for Bcl-2-positive cases to present ER+/low-S-phase/C-erbB-2-negative phenotypes. In terms of distant-recurrence-free survival, those patients expressing Akt-1+/ Bcl-2+ survived longer than Akt-1+/Bcl-2- patients (P = 0.028) while no benefit was observed for Bcl-2 (P = 0.6) or Akt-1 (P = 0.9) individually.

Conclusions

The results suggest that Akt-1 might reinforce the prognostic value of Bcl-2, and probably this phenotype characterises a subgroup of patients less prone to undergo metastasis.