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Phosphorylated c-Src in the nucleus is associated with improved patient outcome in ER-positive breast cancer.

Campbell EJ, McDuff E, Tatarov O, Tovey S, Brunton V, Cooke TG, Edwards J - Br. J. Cancer (2008)

Bottom Line: High level of nuclear activated Src was significantly associated with improved overall survival (P=0.047) and lower recurrence rates on tamoxifen (P=0.02).Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (P<0.05).On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (P=0.004).

View Article: PubMed Central - PubMed

Affiliation: Division of Cancer Sciences and Molecular Pathology, Department of Surgery, Glasgow Royal Infirmary, Glasgow, UK.

ABSTRACT
Elevated c-Src protein expression has been shown in breast cancer and in vitro evidence suggests a role in endocrine resistance. To investigate whether c-Src is involved in endocrine resistance, we examined the expression of both total and activated c-Src in human breast cancer specimens from a cohort of oestrogen receptor (ER)-positive tamoxifen-treated breast cancer patients. Tissue microarray technology was employed to analyse 262 tumour specimens taken before tamoxifen treatment. Immunohistochemistry using total c-Src and activated c-Src antibodies was performed. Kaplan-Meier survival curves were constructed and log-rank test were performed. High level of nuclear activated Src was significantly associated with improved overall survival (P=0.047) and lower recurrence rates on tamoxifen (P=0.02). Improved patient outcome was only seen with activated Src in the nucleus. Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (P<0.05). On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (P=0.004). This shows that c-Src activity is increased in breast cancer and that activated Src within the nucleus of ER-positive tumours predicts an improved outcome. In ER/PgR-positive disease, activated Src kinase does not appear to be involved in de novo endocrine resistance. Further study is required in ER-negative breast cancer as this may represent a cohort in which it is associated with poor outcome.

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Kaplan–Meier survival curves show (A) overall survival difference between ER+ patients with high (above the median value) and low expression of activated nuclear c-Src (P=0.047); (B) 1−survival curve showing disease recurrence in ER+ patients with high and low expression of activated nuclear c-Src (P=0.02) and (C) overall survival differences between activated c-Src depending on the pattern of nuclear staining. Uniform nuclear staining was significantly associated with improved survival compared with no nuclear staining or only perinuclear (P=0.0153).
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fig3: Kaplan–Meier survival curves show (A) overall survival difference between ER+ patients with high (above the median value) and low expression of activated nuclear c-Src (P=0.047); (B) 1−survival curve showing disease recurrence in ER+ patients with high and low expression of activated nuclear c-Src (P=0.02) and (C) overall survival differences between activated c-Src depending on the pattern of nuclear staining. Uniform nuclear staining was significantly associated with improved survival compared with no nuclear staining or only perinuclear (P=0.0153).

Mentions: High expression level (above the median value) of activated c-Src within the nucleus of tumour cells was significantly associated with improved overall survival (P=0.047) and decreased recurrence in tamoxifen-treated patients (P=0.02), Figure 3A and B. On Cox regression analysis this was not shown to be independent of survival or recurrence. The location of activated c-Src around the nucleus was also significant, tumours with uniform staining had improved outcome in comparison with patients with only perinuclear staining (Figure 3C, P=0.0153). Activated c-Src within the cell cytoplasm was not significantly associated with patient outcome.


Phosphorylated c-Src in the nucleus is associated with improved patient outcome in ER-positive breast cancer.

Campbell EJ, McDuff E, Tatarov O, Tovey S, Brunton V, Cooke TG, Edwards J - Br. J. Cancer (2008)

Kaplan–Meier survival curves show (A) overall survival difference between ER+ patients with high (above the median value) and low expression of activated nuclear c-Src (P=0.047); (B) 1−survival curve showing disease recurrence in ER+ patients with high and low expression of activated nuclear c-Src (P=0.02) and (C) overall survival differences between activated c-Src depending on the pattern of nuclear staining. Uniform nuclear staining was significantly associated with improved survival compared with no nuclear staining or only perinuclear (P=0.0153).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2600702&req=5

fig3: Kaplan–Meier survival curves show (A) overall survival difference between ER+ patients with high (above the median value) and low expression of activated nuclear c-Src (P=0.047); (B) 1−survival curve showing disease recurrence in ER+ patients with high and low expression of activated nuclear c-Src (P=0.02) and (C) overall survival differences between activated c-Src depending on the pattern of nuclear staining. Uniform nuclear staining was significantly associated with improved survival compared with no nuclear staining or only perinuclear (P=0.0153).
Mentions: High expression level (above the median value) of activated c-Src within the nucleus of tumour cells was significantly associated with improved overall survival (P=0.047) and decreased recurrence in tamoxifen-treated patients (P=0.02), Figure 3A and B. On Cox regression analysis this was not shown to be independent of survival or recurrence. The location of activated c-Src around the nucleus was also significant, tumours with uniform staining had improved outcome in comparison with patients with only perinuclear staining (Figure 3C, P=0.0153). Activated c-Src within the cell cytoplasm was not significantly associated with patient outcome.

Bottom Line: High level of nuclear activated Src was significantly associated with improved overall survival (P=0.047) and lower recurrence rates on tamoxifen (P=0.02).Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (P<0.05).On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (P=0.004).

View Article: PubMed Central - PubMed

Affiliation: Division of Cancer Sciences and Molecular Pathology, Department of Surgery, Glasgow Royal Infirmary, Glasgow, UK.

ABSTRACT
Elevated c-Src protein expression has been shown in breast cancer and in vitro evidence suggests a role in endocrine resistance. To investigate whether c-Src is involved in endocrine resistance, we examined the expression of both total and activated c-Src in human breast cancer specimens from a cohort of oestrogen receptor (ER)-positive tamoxifen-treated breast cancer patients. Tissue microarray technology was employed to analyse 262 tumour specimens taken before tamoxifen treatment. Immunohistochemistry using total c-Src and activated c-Src antibodies was performed. Kaplan-Meier survival curves were constructed and log-rank test were performed. High level of nuclear activated Src was significantly associated with improved overall survival (P=0.047) and lower recurrence rates on tamoxifen (P=0.02). Improved patient outcome was only seen with activated Src in the nucleus. Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (P<0.05). On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (P=0.004). This shows that c-Src activity is increased in breast cancer and that activated Src within the nucleus of ER-positive tumours predicts an improved outcome. In ER/PgR-positive disease, activated Src kinase does not appear to be involved in de novo endocrine resistance. Further study is required in ER-negative breast cancer as this may represent a cohort in which it is associated with poor outcome.

Show MeSH
Related in: MedlinePlus