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The ectopic expression of BRCA1 is associated with genesis, progression, and prognosis of breast cancer in young patients.

ABSTRACT: OBJECTIVE: The study is to explore the histopathological features and the molecular marker expression of young women with breast cancers. METHODS: The pathological data of 367 cases of female breast cancer patients were retrospectively analyzed, focusing on the analysis of young breast cancer incidence trends and the clinical and pathological features. RESULTS: Compared with elderly breast cancer patients, young women with breast cancers had larger tumor sizes, higher histological grades, and lymph node metastasis rates. The majority of patients were in the PTNM III stage, with the clinical and pathological features of strong invasiveness. The positive expression rate of the BRCA1 protein in the young group was higher than that in the old group. BRCA1 expression was positively correlated with the PTNM stage and axillary lymph node metastasis (P < 0.05). CONCLUSIONS: The ectopic expression of BRCA1 is associated with the genesis, progression, and prognosis of young breast cancer patients. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1628000054838044.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC3541118 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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The ectopic expression of BRCA1 is associated with genesis, progression, and prognosis of breast cancer in young patients.

Zhang Qingli Q Zhang Qinghui Q Cong Hua H Zhang Xiaoli X

Diagnostic pathology 20121231

<h4>Objective</h4>The study is to explore the histopathological features and the molecular marker expression of young women with breast cancers.<h4>Methods</h4>The pathological data of 367 cases of female breast cancer patients were retrospectively analyzed, focusing on the analysis of young breast cancer incidence trends and the clinical and pathological features.<h4>Results</h4>Compared with elderly breast cancer patients, young women with breast cancers had larger tumor sizes, higher histolog ...[more]

PMID: 23276146

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Project description:Since BRCA1 associated breast cancers are frequently classified as hormone receptor negative or even triple negative, the application of endocrine therapies is rather limited in these patients. Like hormone receptors that bind to estrogen or progesterone, thyroid hormone receptors (TRs) are members of the nuclear hormone receptor superfamily. TRs might be interesting biomarkers - especially in the absence of classical hormone receptors. The current study aimed to investigate whether TRs may be specifically expressed in BRCA1 associated cancer cases and whether they are of prognostic significance in these patients as compared to sporadic breast cancer cases. This study analyzed TRα and TRβ immunopositivity in BRCA1 associated (n = 38) and sporadic breast cancer (n = 86). Further, TRs were studied in MCF7 (BRCA1 wildtype) and HCC3153 (BRCA1 mutated) cells. TRβ positivity rate was significantly higher in BRCA1 associated as compared to sporadic breast cancers (p = 0.001). The latter observation remained to be significant when cases that had been matched for clinicopathological criteria were compared (p = 0.037). Regarding BRCA1 associated breast cancer cases TRβ positivity turned out to be a positive prognostic factor for five-year (p = 0.007) and overall survival (p = 0.026) while TRα positivity predicted reduced five-year survival (p = 0.030). Activation of TRβ resulted in down-modulation of CTNNB1 while TRα inhibition reduced cell viability in HCC3153. However, only BRCA1 wildtype MCF7 cells were capable of rapidly degrading TRα1 in response to T3 stimulation. Significantly, this study identified TRβ to be up-regulated in BRCA1 associated breast cancer and revealed TRs to be associated with patients' prognosis. TRs were also found to be expressed in triple negative BRCA1 associated breast cancer. Further studies need to be done in order to evaluate whether TRs may become interesting targets of endocrine therapeutic approaches, especially when tumors are triple-negative.

Project description:BackgroundA role for neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4) in tumorigenesis has been suggested. However, information is lacking on its role in breast tumor biology. The purpose of this study was to determine the role of NEDD4 in the promotion of the growth and progression of breast cancer (BC) and to evaluate the clinicopathologic and prognostic significance of NEDD4.MethodsThe impact of NEDD4 expression in BC cell growth was determined by Cell Counting Kit-8 and colony formation assays. Formalin-fixed paraffin-embedded specimens were collected from 133 adjacent normal tissues (ANTs), 445 BC cases composed of pre-invasive ductal carcinoma in situ (DCIS, n = 37), invasive ductal carcinomas (IDC, n = 408, 226 without and 182 with lymph node metastasis), and 116 invaded lymph nodes. The expression of NEDD4 was analyzed by immunohistochemistry. The association between NEDD4 expression and clinicopathological characteristics was analyzed by chi-square test. Survival was evaluated using the Kaplan-Meier method, and curves were compared using a log-rank test. Univariate and multivariate analyses were performed using the Cox regression method.ResultsNEDD4 promoted BC growth in vitro. In clinical retrospective studies, 16.5% of ANTs (22/133) demonstrated positive NEDD4 staining. Strikingly, the proportion of cases showing NEDD4-positive staining increased to 51.4% (19/37) in DCIS, 58.4% (132/226) in IDC without lymph node metastasis, and 73.1% (133/182) in BC with lymph node metastasis (BCLNM). In addition, NEDD4-positive staining was associated with clinical parameters, including tumor size (P = 0.030), nodal status (P = 0.001), estrogen receptor status (P = 0.035), and progesterone receptor status (P = 0.023). Moreover, subset analysis in BCLNM revealed that high NEDD4 expression correlated with an elevated risk of relapse (P = 0.0276). Further, NEDD4 expression was an independent prognostic predictor. Lastly, the rates for 10-year overall survival and disease-free survival were significantly lower in patients with positive NEDD4 staining than those in BC patients with negative NEDD4 staining BC (P = 0.0024 and P = 0.0011, respectively).ConclusionsNEDD4 expression is elevated in BC and is associated with BC growth. NEDD4 correlated with clinicopathological parameters and predicts a poor prognosis. Thus, NEDD4 is a potential biomarker of poor prognosis and a potential therapeutic target for BC treatment.

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The ectopic expression of BRCA1 is associated with genesis, progression, and prognosis of breast cancer in young patients.

Publications

The ectopic expression of BRCA1 is associated with genesis, progression, and prognosis of breast cancer in young patients.

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