Expression of BRCAI protein in breast cancer and its prognostic significance
Expression of BRCAI protein in breast cancer and its prognostic significance
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DOI：
10.1016/j.humpath.2007.10.011
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发表时间：
2008-06-01
期刊：
影响因子：
3.3
通讯作者：
Ellis, Ian O.
中科院分区：
文献类型：
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作者：
Rakha, Emad A.;El-Sheikh, Sornaia E.;Ellis, Ian O.
BRCA 1是一种肿瘤抑制基因，当突变时，与遗传性乳腺癌的发展有关。在散发性肿瘤中，虽然固有基因突变是罕见的，但由于表达减少或亚细胞定位不正确而导致的BRCA 1缺失被认为是重要的。本研究的目的是检测BRCA 1蛋白的表达和定位，并评估其预后价值，在一系列特征明确的乳腺癌。我们使用组织微阵列和免疫组化检测了一系列浸润性乳腺癌（1940例）中的BRCA 1，以评估其表达模式，并将其与临床病理变量和患者结局相关联。在乳腺癌中，在223例（15%）中观察到核表达完全缺失，在541例（36.6%）乳腺癌中发现胞浆表达。BRCA 1在无特殊类型的导管癌和髓样癌中表达缺失或减少，而在小叶和管状混合癌中表达较少。它还与高级别、晚期淋巴结分期、较大的体积、血管浸润、雌激素受体、孕激素受体和雄激素受体阴性表达、p53和P-cadherin阳性表达以及基底样乳腺癌相关。BRCA 1的改变与较短的无病间隔相关。细胞质表达也与复发和EGFR和HER 2阳性表达的发展相关。它与生存率呈负相关，特别是在低级别、小尺寸和雌激素受体阳性亚组中。在1级亚组中，校正其他预后因素后的多变量分析显示，BRCA 1的胞浆表达是无病期的独立预测因子。BRCA 1基因突变可能在乳腺癌的发生、发展中起重要作用。BRCA 1表达的免疫组化评估可以为乳腺癌的常规分类提供额外的临床相关信息。(C)2008年爱思唯尔公司All rights reserved.
BRCA1 is a tumor suppressor gene which, when mutated, is associated with the development of hereditary breast cancers. In sporadic tumors, although inherent gene mutations are rare, loss of BRCA1, resulting from reduced expression or incorrect subcellular localization, is postulated to be important. The purpose of the current study was to examine the expression and localization of BRCA1 protein and to assess its prognostic value, in a well-characterized series of unselected breast carcinomas. We have examined BRCA1 in a series of invasive breast carcinoma (1940 cases) using tissue microarray and immunohistochemistry, to evaluate its expression pattern and to correlate this with clinicopathologic variables and patient outcome. In breast cancer, complete loss of nuclear expression was observed in 223 cases (15%) and cytoplasmic expression was found in 541 breast cancers (36.6%). Absent or reduced nuclear BRCA1 expression was observed more frequently in ductal carcinoma of no special type and medullary-like carcinoma and less frequently in lobular and tubular mixed carcinomas. It was also associated with high-grade, advanced lymph node stage, larger size, vascular invasion, negative estrogen receptor, progesterone receptor and androgen receptor expression, and positive p53 and P-cadherin expression, and with the basal-like class of breast cancer. Altered BRCA1 was associated with shorter disease-free interval. Cytoplasmic expression was also associated with development of recurrence and positive EGFR and HER2 expression. It showed an inverse association with survival particularly in low-grade, small-size, and estrogen receptor-positive subgroups. In the grade 1 subgroup, multivariate analysis with adjustment for other prognostic factors showed that cytoplasmic expression of BRCA1 was an independent predictor of disease-free interval. BRCA1 alteration may play a significant role in the development and progression of breast cancer. Immunohistochemical assessment of BRCA1 expression could provide additional clinically relevant information in routine classification of breast cancer. (C) 2008 Elsevier Inc. All rights reserved.