乳腺癌BRCA1基因突变及其蛋白表达研究

目的 :探讨散发性乳腺癌的BRCA1基因突变及其蛋白表达与临床病理因素的关系。方法 :收集乳腺癌患者外周血 10 2份、新鲜肿瘤组织 30份 ,分别采用PCR SSCP、DHPLC和基因测序对BRCA1基因第 2、8- 1、8- 2和 2 0外显子进行突变检测 ;对 10 4例肿瘤组织切片进行免疫组化染色标记BRCA1蛋白表达 ,分析免疫组化结果与临床资料的关系。结果 :分别在外显子 8- 1和 8- 2的 2 882 1和 2 8978位点上发现 3例碱基缺失和置换现象。BRCA1蛋白在乳腺癌组织中表达下降 ,且与患者生存状态有关。结论 :在中国散发性乳腺癌患者中BRCA1基因外显子 2、8和 2 0的突变率较低 (2 3% ) ,可以认为在普通中国人群中乳腺癌的发生与该部分碱基序列突变的关系不大 ,但BRCA1蛋白低表达乳腺癌患者复发的危险性增大     

Expression of ER,PR, and Her-2/neu in Endometrial Cancer: A Clinicopathological Study

Objective: To determine any association between expression of estrogen receptor (ER), progesterone receptor(PR), and Her-2/neu and clinicopathological features, including survival, of endometrial carcinoma (EMC)patients. Methods: Samples of formalin-fixed, paraffin-embedded tissue of 108 patients with EMC treated atour institution between January 1994 and December 2007 were immunohistochemically studied. Results: ER,PR, and Her-2/neu expression were positive in 59.3%, 65.7% and 2.8% of cases, respectively. Positive ERexpression was significantly associated with grade I-II tumor while PR expression was linked with endometrioidhistology, grade I-II tumor, less myometrial invasion (MI) and negative lymph node involvement. Her-2/neuexpression was significantly associated with deep MI, while positive ER and negative Her-2/neu expression incombination was significantly associated with longer disease-free and overall survival. Conclusion: ER expressionis a good prognostic factor while Her-2/neu expression appears to be a poor indicator for both disease-free andoverall survival, while PR tended to show favorable influence for only disease-free survival of Thai EMCs.     

BRCA1 Promoter Methylation and Expression - Associations with ER+, PR+ and HER2+ Subtypes of Breast Carcinoma

Introduction: Considering the increasing trend in incidence rates, morbidity and mortality of breast cancer, there is an urgent need to identify and validate new biomarkers for early detection and better management. The purpose of the study was to investigate BRCA1 protein expression and promoter methylation of the BRCA1 gene and their association with molecular subtypes based on estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) positivity. Materials and Methods: A total of 114 breast cancer tissue biopsies were collected for methylation specific PCR (MSP) and immunohistochemical (IHC) analysis. Results: Seven tissue microarrays were constructed. BRCA1 protein expression was reduced in 55/114 (48.2%) and in the majority of ER-negative tumors (73.3%) (p<0.001). Similarly BRCA1 expression was reduced in the majority of PR-negative tumors (69.2%) but without statistical significance (p value=0.083). BRCA1 methylation was positive in 59.6% cases. A subset regarding ER+, PR+ and HER2+ was identified which consisted of 31.6% in which an inverse relationship between BRCA1 methylation and protein expression was noted. Conclusion: Reduced expression was associated with ER and PR negative status which is linked with a poor prognosis. BRCA1 protein expression might thus be used as a prognostic indicator to predict treatment response to hormone therapy.     

Immunohistochemical Analysis of ER,PR, Her2 and CK5/6 in Infiltrative Breast Carcinomas in Indian Patients

Aim: Breast cancer is biologically a heterogeneous disease. Patients with the same diagnostic profile havemarkedly different clinical outcomes. Gene expression studies identified distinct breast cancer subtypes thatdiffer in prognosis. Aim is to identify the immunohistochemical subtypes of breast carcinoma and correlate theresults with pathological features associated with adverse prognosis in our study population. Method: We included107 consecutive cases of invasive breast carcinoma and sub classified using immunohistochemical staining forER, PR, Her2, and CK5/6 into the following subtypes: luminal A, luminal B, basal-like, Her2+ and unclassified.Associations between tumor subtypes and tumor characteristics were examined. Results: The proportion ofeach subtype in our patient population was: luminal A 37.4%, luminal B 11.1%, Her2+ 29% and basal-like7.5%. The following variables were significantly associated with IHC breast cancer subtypes: patient age (p<.05),overall histopathology grade (p<0.001), nuclear grade (p<0.005) and mitotic index (p<0.001). Her2+ and basallike subtypes were associated with poor differentiation (p<0.01), higher nuclear grade (p<0.05) and high mitoticindex (p<0.05). Conclusions: Our data show a higher proportion of patients in the study population undergototal mastectomy and harbor poorly differentiated, node positive tumors than reported. There was also a relativelyhigh percentage of the Her2+ subtype (29%).     

散发性乳腺癌中影响BRCA1蛋白失表达的参数分析

目的: 探讨影响散发性乳腺癌中乳腺癌易感基因(BRCA1)蛋白表达的因素与临床病理指标的相关性。 方法: 免疫组织化学SP法检测乳腺良性病变组织和散发性乳腺癌组织中BRCA1、ERα和HER-2的表达,收集患者临床资料,通过Spearman相关分析和校正的Pearsonχ²检验进行统计分析。 结果: 在良性乳腺病变组织中,BRCA1和ERα蛋白在细胞核的阳性表达率分别为100.0%(20/20)和80.0%(16/20),HER-2在细胞膜阳性表达率为15.0%(3/20);在散发性乳腺癌组织中,BRCA1和ERα蛋白在细胞核阳性表达率分别为57.5%(88/153)和64.1%(98/153),HER-2在细胞膜阳性表达率为34.0%(52/153);与良性乳腺病变组织比较,乳腺癌组织中BRCA1阳性表达率明显降低,差异显著(P<0.05),ERα和HER-2表达率差异不显著(P>0.05)。蛋白表达相关分析及患者临床资料分析表明:BRCA1失表达与ERα失表达相关、与HER-2过表达相关,ERα失表达与HER-2过表达相关;在HER-2过表达、ERα失表达的癌组织中BRCA1失表达率最高;BRCA1失表达与患者高发病年龄、腋淋巴结转移相关,而与乳腺癌病理类型无明显相关。 结论: 在散发性乳腺癌组织中,BRCA1蛋白失表达与ERα失表达、HER-2过表达、患者年龄较高及伴有腋淋巴结转移等相关,BRCA1蛋白失表达参与散发性乳腺癌的发生发展。     

BRCA1 and BRCA2 Common Mutations in Iranian Breast Cancer Patients: a Meta Analysis

Background: To date several common mutations in BRCA1 and BRCA2 associated with breast cancer havebeen reported in different populations. However, the common BRCA1 and BRCA2 mutations among breastcancer patients in Iran have not been described in detail. Materials and Methods: To comprehensively assessthe frequency and distribution of the most common BRCA1 and BRCA2 mutations in Iranian breast cancerpatients, we conducted this meta-analysis on 13 relevant published studies indentified in a literature searchon PubMed and SID. Results: A total of 11 BRCA1 and BRCA2 distinct common mutations were identified,reported twice or more in the articles, of which 10 (c.2311T>C, c.3113A>G, c.4308T>C, c.4837A>G, c.2612C>T,c.3119G>A, c.3548A>G, c.5213G>A c.IVS16-92A/G, and c.IVS16-68A/G) mutations were in BRCA1, and 1(c.4770A>G) was in BRCA2. The mutations were in exon 11, exon 13, intron 16, and exon 20 of BRCA1 andexon 11 of BRCA2. All have been previously reported in different populations. Conclusions: These meta analysisresults should be helpful in understanding the possibility of any first true founder mutation of BRCA1/BRCA2in the Iranian population. In addition, they will be of significance for diagnostic testing, genetic counseling andfor epidemiological studies.     

Effect of Prior Bilateral Oophorectomy on the Presentation of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers

Purpose

To compare the presentation of invasive breast cancer in BRCA1 and BRCA2 mutation carriers with and without prior bilateral oophorectomy.

Patients and methods

Women with a BRCA1 or BRCA2 mutation with the diagnosis of invasive breast cancer were identified from ten cancer genetics clinics. The medical history, medical treatment records and pathology reports for the breast cancers were reviewed. Information was abstracted from medical charts, including history (and date) of oophorectomy, date of breast cancer diagnosis, stage of disease, and pathologic characteristics of the breast cancer. Women with prior bilateral oophorectomy were matched by age, year of diagnosis, and mutation with one or more women who had two intact ovaries at the time of breast cancer diagnosis. Characteristics of the breast tumours were compared between the two groups.

Results

Women with prior bilateral oophorectomy presented with smaller tumours on average compared to women without prior oophorectomy (mean size 1.50 cm vs. 1.95 cm; p = 0.01). Additionally, although not statistically significant, women with intact ovaries were more likely to have high-grade tumour (70% vs. 54%: p = 0.10) and to have positive lymph nodes (34% vs. 18%; p = 0.11) compared to women with prior bilateral oophorectomy.

Conclusions

Bilateral oophorectomy prior to breast cancer appears to favourably influence the biological presentation of breast cancer in BRCA1 and BRCA2 mutation carriers.

     

乳腺癌原发灶与复发转移灶间ER、PR、HER-2、COX-2表达差异分析

[目的]回顾性分析乳腺癌原发灶与转移灶中ER、PR、HER-2、COX-2表达的情况及临床意义。[方法]应用免疫组化的方法,检测了50例乳腺癌转移患者的ER、PR、HER-2、COX-2在原发灶与复发转移灶中的表达。[结果]乳腺癌原发灶与复发转移灶中ER阳性表达分别为70%和38%,有显著性差异(P=0.002)。PR、HER-2、COX-2在乳腺癌原发灶与复发转移灶中的表达差异无统计学意义(P>0.05)。原发灶与转移灶中HER-2与COX-2表达呈相关性(P<0.05)。[结论]乳腺癌原发灶和转移灶中ER、PR、HER-2、COX-2表达不一致,需根据转移灶受体的表达情况决定治疗方案。     

Cancer risks among BRCA1 and BRCA2 mutation carriers

BRCA1 and BRCA2 mutations increase breast and ovarian cancer risks substantially enough to warrant risk reduction surgery, despite variable risk estimates. Underlying this variability are methodological issues, and also complex genetic and nongenetic effects. Although many modifying factors are unidentified, known factors can already be incorporated in individualised risk prediction.     

Challenges and Considerations on Risk-Reducing Surgery in BRCA1/2 Patients with Advanced Breast Cancer

Cancer survivors harboring inherited pathogenic variants in the breast cancer (BC) susceptibility genes BRCA1 or BRCA2 are at increased risk of ovarian cancer (OC) and also of contralateral BC. For these women, risk-reducing surgery (RRS) may contribute to risk management. However, women with locally advanced or metastatic breast cancer (ABC) were excluded from clinical trials evaluating the benefit of these procedures in the BRCA1/2 carriers, and thus, current guidelines do not recommend RRS in this specific setting. Although ABC remains an incurable disease, recent advances in treatment have led to increased survival, which, together with improvement in RRS techniques, raise questions about the potential role of RRS in the management of BRCA1/2 ABC patients. When should RRS be discussed as an option for BRCA1/2 patients diagnosed with ABC? To address this issue, we report two clinical cases that reflect new challenges in routine oncology practice. Team experience and patient motivations may shape multidisciplinary decisions in the absence of evidence-based data. A wise rationale may be the analysis of the competing risks of death by a previous ABC against risk of death by a secondary BC or OC, tailored to patient preferences.     

Correlation between HER2 Expression and Clinicopathological Features of Breast Cancer: A Cross- Sectional Study in Vietnam

Background: HER2 is the target of the therapeutic agents which are used to treat HER2-positive breast cancer. Reports have shown that the HER2 oncogene expression and its association with clinicopathological factors remain unclear in breast cancer (BC) patients.  This study aimed to determine the correlation between HER2 expression and clinicalpathological characteristics of breast cancer in Vietnamese women. Methods: Between June 2016 and August 2018, paraffin-embedded specimens from 237 patients with primary invasive breast carcinoma in Hue University Hospital and Hue Center Hospital, Hue city, Vietnam were examined for pathological features. The gene expression of HER2, ER, PR and Ki-67 were determined by immunohistochemistry (IHC). The gene amplification of Her2 was assessed by using Dual color in situ hybridization (DISH). Results: The most frequent histological type was invasive carcinoma of no special type (NST) with 77.35%, the highest percentage of patients with Grade II was detected (59.36%), tumor size > 2 cm accounted for 71.31% of cases, Lymph node metastases were available in 57.86% cases. Most patients were diagnosed at stage II (59.18%). The majority of patients were classified as moderate Nottingham prognostic index (54.9%). Estrogen receptor and Progesterone receptor were positive in 53.16% and 50.63%, respectively. 76.37% of cases were in high expression group of Ki-67 (≥14%). HER2 IHC 2+, 3+ were accounted for 28.69% and HER2 gene amplification was detected in 31% cases. HER2 gene amplification and/or overexpression was significantly associated with cell proliferation index Ki67. Furthermore, HER2 gene expression tended to be more frequently found in tumors with large tumor size, high grade, high stage and high Nottingham prognostic index and confirmed their prognostic independent role. Conclusions: Our data indicated that HER2 gene expression was significantly correlated with cell proliferation index Ki67, but not significantly associated with another clinicopathological factors in breast cancer of Vietnamese women.     

散发性甲状腺癌中BRCA1和BRCA2的表达情况

目的 探讨乳腺癌易感基因1(breast cancer susceptibility gene 1,BRCA1)和乳腺癌易感基因2(breast canc-er susceptibility gene 2,BRCA2)在散发性甲状腺癌中的表达和意义.方法 应用免疫组化法,检测散发性甲状腺癌中BRCA1和BRCA2的表达...     

c-erbB-2在不同乳腺病变组织中的表达及其临床意义的研究

目的 :探讨c erbB 2癌基因蛋白在乳腺组织中的表达及对乳腺癌早期诊断的价值。方法 :采用免疫组化方法检测 170例不同乳腺病变的c erbB 2表达水平。结果 :c erbB 2癌基因的表达与腋淋巴结转移 (P <0 .0 1)和乳腺癌组织学类型有关 ,特别是它在癌前病变中有表达。结论 :c erbB 2癌基因蛋白既可做为乳腺癌早期诊断指标 ,也可作为预后因素的判断。     

Association of BRCA1 Promoter Methylation with Breast Cancer in Asia: A Meta- Analysis

Objective: The aim of this study was to determine the degree of association of BRCA1 promoter methylation withbreast cancer in Asia. Methods: The study sample for the present meta-analysis was provided by published researcharticles on associations of BRCA1 promoter methylation with breast cancer in Asia accessed through databases onPubMed, ProQuest and EBSCO published between 1997 and November 2017. Pooled odds ratios (OR) were calculatedwith fixed and random-effect models. Data were processed using Review Manager 5.3 (RevMan 5.3). Results: Ofa total of 475 articles, 11 studies were included in our systematic review with meta-analysis of relevant data. Theresults showed a highly significant association between BRCA1 promoter methylation with breast cancer in Asia(OR = 8.78 [95% CI 4.15-18.56, p < 0.00001]). Conclusion: This analysis confirmed association between BRCA1promoter methylation and breast cancer in Asia. BRCA1 promoter assessment might be a predictive or diagnostic aidfor breast cancer prediction.     

乳腺癌中PS2蛋白表达与ER,PR及预后的关系

探讨ＰＳ２蛋白在乳腺癌中的表达及其与ＥＲ、ＰＲ和患者预后的关系,方法应用ＬＳＡＢ免疫组织化学方法检测ＰＳ２蛋白在１０５例乳腺癌中的表达。结果ＰＳ２在乳腺癌中的表达率为５０．４８％（５３／１０５）。４３例ＥＲ和ＰＲ均为阳性者中,有３３例ＰＳ２表达阳性,阳性率为７６．７４％（３３／４３）;而４０例ＥＲ和ＰＲ均为阴性者中,仅有９例呈ＰＳ２表达阳性,阳性率为２２．５０％（９／４０,Ｐ〈０．０１。生存５年以