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A role for BRCA1 in sporadic breast cancer.

Fraser JA, Reeves JR, Stanton PD, Black DM, Going JJ, Cooke TG, Bartlett JM - Br. J. Cancer (2003)

Bottom Line: Intense labelling predicted decreased overall survival (P=0.012), disease-free survival (P=0.029), oestrogen receptor negativity (P=0.0004) and c-erbB-2 overexpression (P=0.006).BRCA1 protein is postulated to function as a tumour suppressor.BRCA1 protein appears to have a significant role in both sporadic and hereditary breast cancers.

View Article: PubMed Central - PubMed

Affiliation: University Department of Surgery, Glasgow Royal Infirmary, Glasgow, UK.

ABSTRACT
To test the hypothesis that altered expression of BRCA1 protein may play an important role in sporadic breast cancer development, 50 randomly selected primary breast cancers (frozen sections, 5 years' median follow-up) were immunolabelled with two monoclonal BRCA1 antibodies (MS110 and MS13). MS110 labelling was exclusively nuclear showing no relation to outcome or tumour pathology. Western blotting demonstrated crossreactivity, suggesting antibody nonspecificity. MS13 labelling was predominantly cytoplasmic. Intense labelling predicted decreased overall survival (P=0.012), disease-free survival (P=0.029), oestrogen receptor negativity (P=0.0004) and c-erbB-2 overexpression (P=0.006). Western blotting detected a 110 kDa molecule consistent with BRCA1 delta11b splice variant. BRCA1 protein is postulated to function as a tumour suppressor. We demonstrate cytoplasmic localisation in sporadic breast cancer suggesting excess delta11b splice variant production, reduced production of full-length BRCA1 and thus postulate reduced tumour suppressor activity. BRCA1 protein appears to have a significant role in both sporadic and hereditary breast cancers.

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Related in: MedlinePlus

(A) Survival curve analysis (from all causes) according to low and high immunohistochemical labelling with the MS13 antibody and (B) disease-free survival curve analysis (local and distant recurrence). Arrowheads indicate censored events (Kaplan–Meier estimates and log-rank tests).
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fig3: (A) Survival curve analysis (from all causes) according to low and high immunohistochemical labelling with the MS13 antibody and (B) disease-free survival curve analysis (local and distant recurrence). Arrowheads indicate censored events (Kaplan–Meier estimates and log-rank tests).

Mentions: Univariate survival analysis was carried out for both sets of data using Kaplan–Meier estimates and log-rank tests. MS110 immunostaining did not relate to disease-free (P=0.62) or overall survival (P=0.62) in this group. However, high MS13 histoscores were associated significantly with both a shorter overall survival (P=0.012; Figure 3AFigure 3


A role for BRCA1 in sporadic breast cancer.

Fraser JA, Reeves JR, Stanton PD, Black DM, Going JJ, Cooke TG, Bartlett JM - Br. J. Cancer (2003)

(A) Survival curve analysis (from all causes) according to low and high immunohistochemical labelling with the MS13 antibody and (B) disease-free survival curve analysis (local and distant recurrence). Arrowheads indicate censored events (Kaplan–Meier estimates and log-rank tests).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747570&req=5

fig3: (A) Survival curve analysis (from all causes) according to low and high immunohistochemical labelling with the MS13 antibody and (B) disease-free survival curve analysis (local and distant recurrence). Arrowheads indicate censored events (Kaplan–Meier estimates and log-rank tests).
Mentions: Univariate survival analysis was carried out for both sets of data using Kaplan–Meier estimates and log-rank tests. MS110 immunostaining did not relate to disease-free (P=0.62) or overall survival (P=0.62) in this group. However, high MS13 histoscores were associated significantly with both a shorter overall survival (P=0.012; Figure 3AFigure 3

Bottom Line: Intense labelling predicted decreased overall survival (P=0.012), disease-free survival (P=0.029), oestrogen receptor negativity (P=0.0004) and c-erbB-2 overexpression (P=0.006).BRCA1 protein is postulated to function as a tumour suppressor.BRCA1 protein appears to have a significant role in both sporadic and hereditary breast cancers.

View Article: PubMed Central - PubMed

Affiliation: University Department of Surgery, Glasgow Royal Infirmary, Glasgow, UK.

ABSTRACT
To test the hypothesis that altered expression of BRCA1 protein may play an important role in sporadic breast cancer development, 50 randomly selected primary breast cancers (frozen sections, 5 years' median follow-up) were immunolabelled with two monoclonal BRCA1 antibodies (MS110 and MS13). MS110 labelling was exclusively nuclear showing no relation to outcome or tumour pathology. Western blotting demonstrated crossreactivity, suggesting antibody nonspecificity. MS13 labelling was predominantly cytoplasmic. Intense labelling predicted decreased overall survival (P=0.012), disease-free survival (P=0.029), oestrogen receptor negativity (P=0.0004) and c-erbB-2 overexpression (P=0.006). Western blotting detected a 110 kDa molecule consistent with BRCA1 delta11b splice variant. BRCA1 protein is postulated to function as a tumour suppressor. We demonstrate cytoplasmic localisation in sporadic breast cancer suggesting excess delta11b splice variant production, reduced production of full-length BRCA1 and thus postulate reduced tumour suppressor activity. BRCA1 protein appears to have a significant role in both sporadic and hereditary breast cancers.

Show MeSH
Related in: MedlinePlus