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The Expression of BRCA1 in Basal-like Breast Cancer and Its Relationship with ID4

Author: XiaoZuo
Tutor: FanQinHe
School: Nanjing Medical University
Course: Pathology
Keywords: Breast Cancer Molecular typing Basaloid type BRCA1 ID4 ER
CLC: R737.9
Type: Master's thesis
Year: 2009
Downloads: 23
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Abstract


Background and purpose of the gene expression profile of breast cancer is divided into different molecular subtypes different subtypes have different pathological features and clinical outcome. Basal-like breast cancer (basal-like breast cancer) is a new identification of breast cancer molecular subtypes, with basal cell phenotype, such as expression basaloid keratin basaloid breast cancer recurrence rate is low, the prognosis is poor . Basal-like breast cancer research data mainly from Western countries, epidemiological studies of rare for basal-like breast cancer in the Chinese population. The molecular mechanisms of basal-like breast cancer is unclear, BRCA1 mutations in hereditary breast cancer usually presents basaloid type, suggesting that the BRCA1 gene and its mediated pathway abnormalities may be associated with the occurrence of basal-like breast cancer. The purpose of this study is to (1) basaloid breast cancer tissue microarray and immunohistochemical methods on a large sample cases of invasive breast cancer molecular typing, described in Chinese breast cancer population distribution and clinical and pathological features. (2) immunohistochemistry and in situ hybridization to detect the expression levels of BRCA1 in the basal-like type breast cancer, and to analyze the relationship between and ID4 expression, to explore the role of the BRCA1 gene and pathway in basal-like subtype of breast cancer in basaloid breast cancer awareness and research specific therapeutic targets provide a theoretical basis for deepening. Method 1. Collect 13 of 1452 cases of breast cancer specimens produced by tissue microarray. Immunohistochemistry to detect ER, HER2, CK5 / 6, EGFR expression, according to the Nielsen standard molecular typing and analysis of the incidence of basal-like breast cancer and the clinical and pathological features. 3 immunohistochemical methods to detect molecular subtypes of breast cancer in BRCA1 and ID4 expression levels. 4. Situ hybridization method for detection breast cancer molecular subtypes BRCA1mRNA of expression. . Basal-like breast cancer incidence rate of breast cancer population of China 17.0%, with the age of onset of light, large tumor size and axillary lymph node metastases is low, and high histological grade. Basaloid breast cancer BRCA1 protein expression was 63.0% (136/216), lower than the ER-positive breast luminal A type (P lt; 0.001) and luminal B-type (P lt; 0.001) with other subtypes of ER-negative breast cancer (HER2 overexpression type and bare expression type) the difference was not statistically significant. BRCA1mRNA positive expression rate was 30.0%, lower than the other type of breast cancer (except with HER2 over-expression of type P value lt; outside 0.01, P value lt; 0.001). 3. ID4 protein expression rate in the basal-like breast were 64.6% (117/181), higher than the ER-positive breast glandular A type (P lt; 0.001) and luminal B-type (P lt; 0.01) with ER-negative breast cancer subtypes (HER2 expression type and the bare expression type) the difference was not statistically significant. ID4 protein positive expression of ER positive expression was negatively correlated (r = -0.202, P lt; 0.001). 4. BRCA1 protein expression of ER-positive expression was positively correlated (r = 0.254, P lt; 0.001), with ID4 expression was negatively correlated (r = -0.261, P lt; 0.001), BRCA1 protein expression of CK5 / 6 and EGFR expression was not correlated. Conclusion 1. Basaloid breast cancer has unique clinical and pathological features, the incidence of breast cancer population in China and reported similar downregulation of the BRCA1 protein and mRNA in the basal-like breast dysfunction may be involved in occurrence of basal-like breast cancer. 3.ID4 highly expressed in the basal-like breast ID4 protein expression of BRCA1 expression was negatively correlated. ID high expression may be one of the reasons for BRCA1 downregulation in the basal-like breast. 4. BRCA1 was positively correlated with the expression of ER-positive ID4 ER-positive expression was negatively correlated ER may be involved in the molecular mechanisms regulating the expression of BRCA1 and ID4.

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