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Akt kinases in breast cancer and the results of adjuvant therapy.

Stål O, Pérez-Tenorio G, Akerberg L, Olsson B, Nordenskjöld B, Skoog L, Rutqvist LE - Breast Cancer Res. (2003)

Bottom Line: The benefit from tamoxifen was analysed in oestrogen receptor (ER)-positive patients.Patients with a negative status of Akt (no overexpression of Akt1, Akt2 or pAkt) showed significant benefit from tamoxifen.The difference in rate ratio did not reach statistical significance.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedicine and Surgery, Division of Oncology, Faculty of Health Sciences, Linköping University, Linköping, Sweden. olle.stal@onk.liu.se

ABSTRACT

Background: The serine/threonine kinase Akt, or protein kinase B, has recently been a focus of interest because of its activity to inhibit apoptosis. It mediates cell survival by acting as a transducer of signals from growth factor receptors that activate phosphatidylinositol 3-kinase.

Methods: We analysed the expression of the isoforms Akt1 and Akt2 as well as phosphorylated Akt (pAkt) by immunohistochemistry in frozen tumour samples from 280 postmenopausal patients who participated in a randomised trial comparing cyclophosphamide-methotrexate-5-fluorouracil chemotherapy and postoperative radiotherapy. The patients were simultaneously randomised to tamoxifen or to no endocrine treatment.

Results: Marked staining was found in 24% of the tumours for Akt1, but in only 4% for Akt2. A low frequency of Akt2-positive cells (1-10%) was observed in another 26% of the tumours. pAkt was significantly associated with both Akt1 and Akt2 expression. Overexpression of erbB2 correlated significantly with pAkt (P = 0.0028). The benefit from tamoxifen was analysed in oestrogen receptor (ER)-positive patients. Patients with a negative status of Akt (no overexpression of Akt1, Akt2 or pAkt) showed significant benefit from tamoxifen. The relative rate of distant recurrence, with versus without tamoxifen, was 0.44 (95% confidence interval [CI], 0.25-0.79) for ER+/Akt1- patients, while it was 0.72 (95% CI, 0.34-1.53) for ER+/Akt1+ patients. The difference in rate ratio did not reach statistical significance. The rate of locoregional recurrence was significantly decreased with radiotherapy versus chemotherapy for Akt-negative patients (rate ratio, 0.23; 95% CI, 0.08-0.67; P = 0.0074), while no benefit was evident for the Akt-positive subgroup (rate ratio, 0.77; 95% CI, 0.31-1.9; P = 0.58). The interaction between Akt and the efficacy of radiotherapy was significant in multivariate analysis (P = 0.042).

Conclusion: Activation of the Akt pathway is correlated with erbB2 overexpression in breast cancer. The results suggest that Akt may predict the local control benefit from radiotherapy.

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Related in: MedlinePlus

Immunostaining of (a, b) Akt1, (c) Akt2 and (d) phosphorylated Akt.
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Figure 1: Immunostaining of (a, b) Akt1, (c) Akt2 and (d) phosphorylated Akt.

Mentions: The results of the immunostaining for Akt1, Akt2 and pAkt are presented in Table 2. All three forms exhibited cytoplasmic staining, to some extent localised to the cell membrane (Fig. 1). The staining patterns for Akt1 and Akt2 were different. In the immunopositive tumours, Akt1 was frequently expressed in a high percentage of cells, whereas the staining of Akt2 was mostly sparse. Most normal cells were negative for the Akt kinases. However, the basal cells of ductal structures stained positive for Akt1.


Akt kinases in breast cancer and the results of adjuvant therapy.

Stål O, Pérez-Tenorio G, Akerberg L, Olsson B, Nordenskjöld B, Skoog L, Rutqvist LE - Breast Cancer Res. (2003)

Immunostaining of (a, b) Akt1, (c) Akt2 and (d) phosphorylated Akt.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC154147&req=5

Figure 1: Immunostaining of (a, b) Akt1, (c) Akt2 and (d) phosphorylated Akt.
Mentions: The results of the immunostaining for Akt1, Akt2 and pAkt are presented in Table 2. All three forms exhibited cytoplasmic staining, to some extent localised to the cell membrane (Fig. 1). The staining patterns for Akt1 and Akt2 were different. In the immunopositive tumours, Akt1 was frequently expressed in a high percentage of cells, whereas the staining of Akt2 was mostly sparse. Most normal cells were negative for the Akt kinases. However, the basal cells of ductal structures stained positive for Akt1.

Bottom Line: The benefit from tamoxifen was analysed in oestrogen receptor (ER)-positive patients.Patients with a negative status of Akt (no overexpression of Akt1, Akt2 or pAkt) showed significant benefit from tamoxifen.The difference in rate ratio did not reach statistical significance.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedicine and Surgery, Division of Oncology, Faculty of Health Sciences, Linköping University, Linköping, Sweden. olle.stal@onk.liu.se

ABSTRACT

Background: The serine/threonine kinase Akt, or protein kinase B, has recently been a focus of interest because of its activity to inhibit apoptosis. It mediates cell survival by acting as a transducer of signals from growth factor receptors that activate phosphatidylinositol 3-kinase.

Methods: We analysed the expression of the isoforms Akt1 and Akt2 as well as phosphorylated Akt (pAkt) by immunohistochemistry in frozen tumour samples from 280 postmenopausal patients who participated in a randomised trial comparing cyclophosphamide-methotrexate-5-fluorouracil chemotherapy and postoperative radiotherapy. The patients were simultaneously randomised to tamoxifen or to no endocrine treatment.

Results: Marked staining was found in 24% of the tumours for Akt1, but in only 4% for Akt2. A low frequency of Akt2-positive cells (1-10%) was observed in another 26% of the tumours. pAkt was significantly associated with both Akt1 and Akt2 expression. Overexpression of erbB2 correlated significantly with pAkt (P = 0.0028). The benefit from tamoxifen was analysed in oestrogen receptor (ER)-positive patients. Patients with a negative status of Akt (no overexpression of Akt1, Akt2 or pAkt) showed significant benefit from tamoxifen. The relative rate of distant recurrence, with versus without tamoxifen, was 0.44 (95% confidence interval [CI], 0.25-0.79) for ER+/Akt1- patients, while it was 0.72 (95% CI, 0.34-1.53) for ER+/Akt1+ patients. The difference in rate ratio did not reach statistical significance. The rate of locoregional recurrence was significantly decreased with radiotherapy versus chemotherapy for Akt-negative patients (rate ratio, 0.23; 95% CI, 0.08-0.67; P = 0.0074), while no benefit was evident for the Akt-positive subgroup (rate ratio, 0.77; 95% CI, 0.31-1.9; P = 0.58). The interaction between Akt and the efficacy of radiotherapy was significant in multivariate analysis (P = 0.042).

Conclusion: Activation of the Akt pathway is correlated with erbB2 overexpression in breast cancer. The results suggest that Akt may predict the local control benefit from radiotherapy.

Show MeSH
Related in: MedlinePlus