A role for BRCA1 in sporadic breast cancer

Fraser, Jennifer; Reeves, Jonathan R.; Stanton, Peter; Black, D; Going, James J.; Cooke, Tim; Bartlett, John M.S.

doi:10.1038/sj.bjc.6600863

Cited by 40 publications

(29 citation statements)

References 31 publications

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“…However, it is important to mention that some studies evaluating BRCA1 protein expression and prognosis have shown different results. For examples, Taylor et al [11] noted both nuclear and cytoplasmic staining in the majority of normal breast epithelium and lack of correlation between cytoplasmic staining and clinical features; Fraser et al [46] showed no relation to outcome or tumor pathology, however, in their study; MS110 (the antibody used in the current study) showed cross reactivity by Western blotting suggesting antibody nonspecificity.…”

Section: Discussionmentioning

confidence: 89%

Expression of BRCA1 protein in breast cancer and its prognostic significance

Rakha¹,

Elsheikh²,

Kandil³

et al. 2008

Human Pathology

134

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Section: Discussionmentioning

confidence: 89%

Expression of BRCA1 protein in breast cancer and its prognostic significance

Rakha¹,

Elsheikh²,

Kandil³

et al. 2008

Human Pathology

134

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“…Staining was scored blind by two independent observers using a weighted histoscore method (Fraser et al, 2003), interclass correlation coefficients (ICCC) were calculated and confirmed acceptable correlation between observer scores (Armitage and Berry, 1995). ICCC values for histoscores were 0.67 (good) and 0.91 (excellent) for PSA and AR staining, respectively (Armitage and Berry, 1995).…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 90%

Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer

et al. 2003

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This study examined androgen receptor (AR) gene amplification and protein expression in 102 matched paired hormone sensitive and resistant tumours from 51 patients. AR gene amplification and X chromosome copy number were assessed by fluorescent in situ hybridisation, and protein expression was assessed by immunohistochemistry. All tumours were stained for PSA protein expression. Significantly more tumours exhibited AR amplification following the development of hormone resistance (20%, 10 out of 49) compared to matched hormone-sensitive tumours from the same patient (2%, one out of 48) (P ¼ 0.0085). The level of AR expression was significantly higher in hormone-resistant tumours compared to matched hormone-sensitive tumours from the same patient (130, interquartile range, 55 -167 vs 94.5 interquartile range, 55 -120, P ¼ 0.019). AR expression levels in hormone-resistant tumours with and without AR amplification were not significantly different. However, an increase in AR expression was seen with the development of AR amplification in paired tumours. The rate of AR gene amplification and/or an increase in AR protein expression during androgen resistant is too low to wholly explain the development of androgen resistance. Alternative mechanisms for modulating the function of the AR, or other signalling pathways, must be considered as key factors in the development of hormoneresistant prostate.

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“…Tissue staining intensity was scored blind by two independent observers using a weighted histoscore method (Fraser et al, 2003) also known as the Hscore system (McCarty et al, 1986). Histoscores were calculated from the sum of (1 Â % cells staining weakly positive) þ (2 Â % cell staining moderately positive) þ Table 1 shows the median histoscore and interquartile range (IQR) for hormone-sensitive tumours (HSPCs) and hormone-refractory tumours (HRPCs) and the P-values of HSPC histoscores compared to HRPC histoscores using a Wilcoxon signed-rank test.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Phosphorylation of the androgen receptor is associated with reduced survival in hormone-refractory prostate cancer patients

et al. 2008

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Cell line studies demonstrate that the PI3K/Akt pathway is upregulated in hormone-refractory prostate cancer (HRPC) and can result in phosphorylation of the androgen receptor (AR). The current study therefore aims to establish if this has relevance to the development of clinical HRPC. Immunohistochemistry was employed to investigate the expression and phosphorylation status of Akt and AR in matched hormone-sensitive and -refractory prostate cancer tumours from 68 patients. In the hormone-refractory tissue, only phosphorylated AR (pAR) was associated with shorter time to death from relapse (P ¼ 0.003). However, when an increase in expression in the transition from hormone-sensitive to -refractory prostate cancer was investigated, an increase in expression of PI3K was associated with decreased time to biochemical relapse (P ¼ 0.014), and an increase in expression of pAkt 473 and pAR 210 were associated with decreased disease-specific survival (P ¼ 0.0019 and 0.0015, respectively). Protein expression of pAkt 473 and pAR 210 also strongly correlated (Po0.001, c.c. ¼ 0.711) in the hormone-refractory prostate tumours. These results provide evidence using clinical specimens, that upregulation of the PI3K/Akt pathway is associated with phosphorylation of the AR during development of HRPC, suggesting that this pathway could be a potential therapeutic target.

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A role for BRCA1 in sporadic breast cancer

Cited by 40 publications

References 31 publications

Expression of BRCA1 protein in breast cancer and its prognostic significance

Expression of BRCA1 protein in breast cancer and its prognostic significance

Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer

Phosphorylation of the androgen receptor is associated with reduced survival in hormone-refractory prostate cancer patients

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