乳腺癌易感基因1和微管蛋白β3在胃癌中的表达及其临床意义

目的:探讨胃癌患者乳腺癌易感基因1（BRCA1）和微管蛋白β3（TUBB3）的表达及其临床意义,为胃癌的精确诊治提供依据。方法:收集2018年12月至2020年5月在安徽省马鞍山市人民医院住院治疗并且接受胃镜活组织检查或手术的46例胃癌患者资料。采用免疫组织化学法检测胃癌组织和癌旁组织中BRCA1和TUBB3蛋白的表达...     

PTEN蛋白在乳腺癌组织中的表达及其临床意义

目的 探讨抑癌基因PTEN在乳腺癌组织中的表达及其临床意义。方法 采用SABC免疫组织化学方法，检测了62例乳腺癌、15例癌旁及12例正常乳腺组织中PTEN蛋白表达水平，结合临床病理指标进性分析。结果 乳腺癌组PTEN蛋白阳性表达率（56．5％）显著低于癌旁组（86．7％）和正常组（100．0％），P均〈0．05；癌旁组（86．7％）低于正常组（100．0％），P〉0．05。伴有淋巴结转移的乳腺癌中PTEN蛋白阳性表达率（32．1％）显著低于无淋巴结转移乳腺癌（61．8％），P〈0．05；浸润性癌PTEN蛋白阳性表达率（44．4％）显著低于早期浸润性癌（75．0％），P〈0．05；PTEN蛋白表达与肿瘤大小、PTNM分期无关，P〉0．05。结论 PTEN蛋白在乳腺癌的发生、发展、侵袭转移中可能起着重要作用。PTEN蛋白表达水平可以作为判定乳腺癌病理生物学行为的客观指标。     

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102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20外显子进行突变检测；对104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28821和28978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20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。     

热休克蛋白5在乳腺癌组织中的表达及其意义

目的 探讨乳腺癌组织中热休克蛋白5（HSPA5）的表达及其与乳腺癌临床病理因素的关系.方法 对乳腺癌手术切除标本中的癌组织97例以及其中带有癌旁正常组织的标本40例,用免疫组织化学二步法检测HSPA5蛋白表达情况.结果 HSPA5在97例乳腺癌中的阳性表达率为81.4％（79/97）.在所选取的40例乳腺癌及癌旁正常组织中,HSPA5的阳性表达率分别为32.5％（13/40）、7.5％（3/40）,差异有统计学意义（x 2=7.813,P=0.038）.HSPA5在不同组织学类型及不同肿瘤直径乳腺癌中的表达差异均无统计学意义（x2=5.785、1.500,P=0.056、0.296）;而在不同组织学分级和有无淋巴结转移的乳腺癌中,表达差异有统计学意义（x2=22.233、5.342,P=0.007、0.024）.结论 HSPA5的在乳腺癌组织中高表达,可能与乳腺癌的发生、发展和浸润转移有关,对于判断乳腺癌的临床预后有重要意义.     

金属硫蛋白在乳腺癌中的表达及其与预后的关系

试图了解金属硫蛋白（ＭＴ）在乳腺病变中的表达程度及其与预后的关系。方法用３７例良性乳腺病变的切除标本和有随访结果的１４０例乳腺癌标本，经１０％福尔马林固定，用石蜡包埋的切片作ＭＴ免疫组织化学染色。结果ＭＴ在良、恶性乳腺病变中的表达有显著差异（Ｐ＜０．００１）。ＭＴ在乳腺癌中的表达随组织学级别的升高而升高。ＭＴ在肿瘤中的超表达与预后差相关，也与５年生存率密切相关。ＭＴ在肿瘤中的表达与手术时腋下淋巴结有无转移无相关性，但在腋下淋巴结转移的肿瘤伴ＭＴ阳性表达者死亡率高于ＭＴ阴性表达者。结论ＭＴ染色可作为一项新的估计乳腺癌预后有价值的指标。     

乳腺癌ps2 蛋白表达与临床病理关系的研究

 目的　探讨ps2 基因蛋白在乳腺癌的表达及其与临床病理因素的关系。方法　应用免疫组化法检测196 例可手术乳腺癌p s2 基因蛋白表达。对其中26 例有可测量病灶患者给予1～2 周期CMF或FEC 方案新辅助化疗。结果　p s2 基因蛋白表达与ER 密切相关( P < 0. 01) ,与组织学分型及Her22的表达有关( P < 0. 05) 。与新辅助化疗疗效的关系具临界统计学意义( P = 0. 06) 。但与年龄、TNM 分期、原发灶的大小及腋窝淋巴结的状态无关。结论　ps2 基因蛋白表达可作为判断乳腺癌生物学行为的一项指标。     

乳腺癌中KAI1蛋白表达与临床病理特征的相关性

目的:研究KAI1蛋白在人乳腺癌中的表达及其与临床病理特征的相关性。方法:应用免疫组织化学S-P法检测107例乳腺癌及30例癌旁乳腺组织中的KAI1蛋白表达情况。结果:乳腺癌组中KAI1蛋白高表达率显著低于正常乳腺组织(P<0.05)。正常组织及非侵袭性乳腺癌中,KAI1蛋白呈高表达;反之,在浸润性乳腺癌中KAI1表达减少。伴有腋窝淋巴结转移的61例乳腺癌中,KAI1蛋白高表达率为21.3%(13/61),无腋窝淋巴结转移组46例中,KAI1蛋白高表达率为39.0%(18/46),两者差异有显著性(P<0.05)。同时发现KAI1蛋白表达与肿瘤大小、年龄无相关性。结论:在乳腺癌进展过程中,KAI1蛋白表达降低在乳腺癌浸润和转移过程中起着重要的作用,检测KAI1蛋白表达可能成为监测人乳腺癌进展及临床上判断其预后的重要参考指标。     

浸润性乳腺癌组织表达α-5、β-1整合蛋白的临床病理意义

整合蛋白(integrin)是一种特殊的细胞表面膜蛋白,为重要的细胞粘附因子[1～2].它在结构上具有多态性,由α和β二个亚单位构成异源性二聚体复合物,其不同状态的复合物可与不同的粘附蛋白结合.我们最近研究发现,纤维粘连蛋白(fibronectinFN)在乳腺癌细胞外基质(ECM)中占较大比例,并且表达量多与患者预后好有明显关系[3].国外研究证实α-5、β-1整合蛋白是大多数细胞表面较大的FN受体,它与FN之间的相互关系可对恶性肿瘤发生多方面的作用[1～2][4～5].但它在乳腺癌实体瘤中的表达状况及意义还不十分明确.为了进一步证明其作用和意义,我们对α-5、β-1整合蛋白在乳腺癌的表达进行了初步研究和观察.     

乳腺癌易感基因1的临床研究进展

乳腺癌易感基因1(BRCA1)突变与乳腺癌、卵巢癌等许多癌症发生密切相关.近年来越来越多的研究提示,在化疗疗效、放疗敏感性及手术效果等方面,BRCA1突变乳腺癌与其他乳腺癌相比有显著差异.BRCA1的研究为其今后在临床上的应用提供了方向.     

乳腺癌耐药蛋白在乳腺癌组织中的表达及其与预后的关系

目的:研究乳腺癌耐药蛋白(BCRP)在乳腺癌组织中的表达,评估其在乳腺癌预后中的作用。方法:采用免疫组织化学方法(IHC)检测60例手术切除的乳腺癌组织中BCRP的表达,并分析其与临床病理特征的关系及对预后的影响。结果:①BCRP在乳腺癌组织中的阳性表达率为35%(21/60例);②腋淋巴结或激素受体阳性者BCRP表达水平显著高于腋淋巴结阴性者和激素受体阴性者(P<0.05),BCRP表达与年龄、月经状况、肿瘤大小和组织学分级均无关(P>0.05);③Kaplan-Meier生存分析结果表明BCRP表达与无病生存期显著相关(P<0.05),但和总生存期无关(P>0.05);④Cox单因素和多因素分析都显示肿瘤大小、淋巴结转移和雌激素受体(ER)与无病生存期和总生存期显著相关(P<0.05),另外孕激素受体与总生存期(P<0.05)显著相关。结论:BCRP在乳腺癌组织中具有一定的表达水平,与乳腺癌患者的无病生存期有关,而与总生存期无关。     

A role for BRCA1 in sporadic breast cancer

To test the hypothesis that altered expression of BRCA1 protein may play an important role in sporadic breast cancer development, 50 randomly selected primary breast cancers (frozen sections, 5 years' median follow-up) were immunolabelled with two monoclonal BRCA1 antibodies (MS110 and MS13). MS110 labelling was exclusively nuclear showing no relation to outcome or tumour pathology. Western blotting demonstrated crossreactivity, suggesting antibody nonspecificity. MS13 labelling was predominantly cytoplasmic. Intense labelling predicted decreased overall survival (P=0.012), disease-free survival (P=0.029), oestrogen receptor negativity (P=0.0004) and c-erbB-2 overexpression (P=0.006). Western blotting detected a 110 kDa molecule consistent with BRCA1 delta11b splice variant. BRCA1 protein is postulated to function as a tumour suppressor. We demonstrate cytoplasmic localisation in sporadic breast cancer suggesting excess delta11b splice variant production, reduced production of full-length BRCA1 and thus postulate reduced tumour suppressor activity. BRCA1 protein appears to have a significant role in both sporadic and hereditary breast cancers.     

Localization of BRCA1 protein in human breast cancer cells

There is still an ongoing debate concerning the cellular localization of BRCA1 protein in breast cancer. To address this question, we compared the localization of BRCA1 protein using several monoclonal (Ab-1) or polyclonal (C20, D20, I20) antibodies under different technical conditions on human breast cancer cell lines. We worked on the fixation and permeabilization conditions in order to preserve the morphological structures of the cells, as confirmed by transmission electron microscopy studies. As expected from the gene sequence analysis and the biochemical features, both nucleus and cytoplasmic BRCA1 protein staining were detected in cells fixed for 60 min in 4% paraformaldehyde and permeabilized with either 0.3% saponin or 0.02% Triton. In these conditions, the same results were obtained: (i) with the four antibodies tested, (ii) with several dilutions (up to tenfold) of the monoclonal antibody, and (iii) in all the tested breast cancer cell lines. In addition, we validated the functionality of these conditions by quantifying the effects of estrogens and their antagonists on the regulation of BRCA1 protein expression in the MCF7 cell line.     

散发性乳腺癌组织中BRCA1基因启动子甲基化与蛋白表达的相关性

目的：探讨BRCA1基因启动子甲基化对BRCA1蛋白表达的影响,及与散发性乳腺癌发病之间的关系。方法：甲基化特异性PCR（MSP）法检测51例散发性乳腺浸润导管癌和10例乳腺良性组织的BRCA1基因启动子甲基化状态,SP法检测BRCA1蛋白表达水平。结果：10例乳腺良性组织中均未检测到BRCA1启动子的异常甲基化,BRCA1蛋白在细胞核均阳性表达,其中70％（7／10）为强阳性表达。在51例散发性乳腺浸润性导管癌组织中检测到7例（13．73％）BRCAl启动子发生异常甲基化,其余44例（86．27％）未检测到BRCA1启动子甲基化。7例BRCA1启动子甲基化的组织均未见BRCA1蛋白细胞核阳性表达（0／7）,仅有1例BRCA1蛋白细胞质表达;44例未检测到BRCA1启动子甲基化的浸润性导管癌中,30例（68．18％）BRCA1蛋白在细胞核阳性表达,14例（31．82％）BRCA1蛋白在细胞核阴性表达。BRCA1启动子甲基化与BRCA1蛋白核低表达密切相关,X^2=11．9591,P=0．0005;BRCA1蛋白的表达在乳腺良性组织与癌组织之间差异有统计学意义,X^2=4．5879,P=0．032。结论：乳腺癌易感基因BRCA1启动子甲基化可抑制BRCA1蛋白表达,并影响其参与散发性乳腺癌的发生发展过程。     

BRCA1与p53在散发性乳腺癌中的表达

目的探讨BRC1和p53蛋白表达在散发性乳腺癌中的作用。方法采用免疫组织化学S-P法检测86例乳腺癌、86例癌旁组织、48例乳腺增生症手术标本中BRCA1及p53蛋白的表达情况。结果BRCA1表达在乳腺癌、乳腺癌旁组织、乳腺增生症中的阳性率分别为11．6％（10／86）、16．3％（14／86）和100．0％（48／48）,三组比较差异有统计学意义（P〈0．01）;p53在乳腺癌、乳腺癌旁组织、乳腺增生症中的阳性率分别为37．2％（32／86）、16．3％（14／86）和8．3％（4／48）,三组比较差异有统计学意义（P〈0．01）;乳腺癌组织中BRCA1与p53表达之间无显著性相关（r=0．608,P〉0．05）。结论BRCA1和p53蛋白异常表达在散发性乳腺癌发生、发展过程中起着一定作用。     

家族性乳腺癌患者及家系成员乳腺癌易感基因携带情况调查

目的 乳腺癌易感基因1(breast cancer susceptibility gene 1,BRCA1)和BRCA2基因已经证实与家族性乳腺癌密切相关.本研究旨在分析中国汉族家族性乳腺癌患者及家系成员BRCA1和BRCA2突变特征及携带情况.方法 收集2013 12-02-2015-06-08军事医学科学院附属医院确诊的中国汉族家族性乳腺癌患者55例及家系成员48名,共计103例样本.柚取外周静脉血提取DNA,应用聚合酶链反应(polymerase chain reaction,PCR) DNA直接测序方法检测BRCA1和BRCA2基因全编码外显子序列.结果 55例家族性乳腺癌患者中发现5个BRCA基因致病性突变位点,1个突变位点乳腺癌信息库中见报道(BRCA1:4730insG),4个为新发现突变位点(BRCA1:1937insC,4538insAG;BRCA2:1382delA,2820delA).家族性乳腺癌患者BRCA1/2突变率为9.09％(BRCA1,5.45％;BRCA2,3.64％),其中三阴性乳腺癌患者突变率为22.22％(x2 =1.99,P=0.20),早发性乳腺癌患者(≤35岁)突变率为20.00％,x2=0.79,P=0.39.48例家系成员检测到3个新发现突变位点(BRCA1:1370insA,3459insA;BRCA2:6502insT),总突变率为6.25％.结论 中国汉族家族性乳腺癌患者BRCA基因突变率显著低于国外,应重点关注有家族史的三阴性乳腺癌患者和早发性乳腺癌患者;家系成员中发现BRCA基因致病性突变,家系成员突变率和发病风险有待进一步研究,应引起重视.     

Risk of cancer in BRCA1 and BRCA2 mutation-positive and -negative breast cancer families (Finland)

Objectives: To compare the risk of cancer between BRCA1 or BRCA2 mutation-positive and -negative families. Methods: We assessed standardized incidence ratios (SIR) in 107 Finnish breast cancer families (12 BRCA1, 11 BRCA2, 84 non-BRCA1/2) with confirmed genealogy. The observed numbers of cancer cases were compared to the expected ones; both numbers were based on the population-based Finnish Cancer Registry. Results: Risk of ovarian cancer for first-degree relatives was high in BRCA1 (SIR 29, 95% confidence interval 9.4–68) and in BRCA2 families (SIR 18, 8.3–35), but not increased for non-BRCA1/2 families (SIR 1.0, 0.2–2.9). The SIR for subsequent ovarian cancer among breast cancer patients was 61 (20–142), 38 (11–98), and 0 (0–4.2), respectively. The risk of subsequent new breast cancer among breast cancer patients was equally high in BRCA1 families (SIR 11, 3.6–26) and in BRCA2 families (SIR 10, 3.3–24) and somewhat lower in mutation-negative families (SIR 3.7, 2.1–6.1). The risk of breast cancer among relatives was markedly increased in all three groups. The only elevated SIR, besides breast and ovarian, was that for prostate cancer in BRCA2 families (SIR 4.9, 1.8–11). Conclusions: The excess risk of breast cancer in non-BRCA1/2 families suggests the existence of another predisposition gene which seems not to be linked with increased risk of ovarian cancer.     

BRCA1和BRCA2基因与乳腺癌相关的研究进展

BRCA1和BRCA2基因是与乳腺癌尤其是遗传性乳腺癌发生发展密切相关的抑癌基因.研究表明,部分乳腺癌患者存在BRCA1和BRCA2基凶突变,而且出现这两个基因突变的乳腺癌表现出不同的病理学特点.通过检测乳腺癌患者BRCA1和BRCA2基因的突变情况,将有助于对乳腺癌患者预后的早期评估.     

Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers

Purpose:

The objective of this study was to estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers; and measure the extent to which host, family history, and cancer treatment-related factors modify the risk.

Patients and methods:

Patients were 810 women, with stage I or II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up.

Results:

Overall, 149 subjects (18.4%) developed a contralateral breast cancer. The 15-year actuarial risk of contralateral breast cancer was 36.1% for women with a BRCA1 mutation and was 28.5% for women with a BRCA2 mutation. Women younger than 50 years of age at the time of breast cancer diagnosis were significantly more likely to develop a contralateral breast cancer at 15 years, compared with those older than 50 years (37.6 vs 16.8% P=0.003). Women aged <50 years with two or more first-degree relatives with early-onset breast cancer were at high risk of contralateral breast cancer, compared with women with fewer, or no first-degree relatives with breast cancer (50 vs 36% P=0.005). The risk of contralateral breast cancer was reduced with oophorectomy (RR 0.47; 95% CI 0.30–0.76; P=0.002).

Conclusion:

The risk of contralateral breast cancer risk in BRCA mutation carriers declines with the age of diagnosis and increases with the number of first-degree relatives affected with breast cancer. Oophorectomy reduces the risk of contralateral breast cancer in young women with a BRCA mutation.     

ICAM基因多态性与BRCA1相互作用对乳腺癌危险度的影响

目的:探讨细胞间黏附分子(ICAM)基因座位单核苷酸多态性(SNPs)与乳腺癌危险度之间的关系,以及这些SNPs位点与BRCA1基因相互作用对乳腺癌危险度的影响。方法:研究对象为1034例女性乳腺癌病例和1091例非恶性肿瘤对照。采外周血提DNA后使用基质辅助激光解吸附电离飞行时间质谱检测技术(MALDI-TOF)对SNPs位点进行基因分型。用χ2检验和Logistic回归模型进行统计学分析。结果:rs1056538位点携带C等位基因对个体患乳腺癌具有保护作用(ORCT=0.3423,95%CI:0.2351～0.4982;ORCC=0.5943,95%CI:0.3899～0.9058),而rs2228615AG和rs281439GG基因型个体则有较高的危险度发生乳腺癌(ORrs2228615AG=2.6771,95%CI:1.4938～4.7976;ORrs281439GG=1.9845,95%CI:1.0287～3.8285)。对于携带BRCA1突变的个体,与全部研究对象所得的结果相比,rs1056538位点携带C等位基因的保护作用更为明显(ORCT=0.2797,95%CI:0.1984～0.3321;ORCC=0.4983,95%CI:0.3942～0.7211),rs2228615位点携带G等位基因的危险度更高(ORAG=3.3369,95%CI:1.9195～5.8009;ORGG=2.0289,95%CI:1.1704～3.5170),而rs281439GG基因型危险度改变不大。结论:ICAM基因座位上SNPs与乳腺癌危险度有关。ICAM基因与BRCA1基因间存在相互作用,影响了乳腺癌的危险度。     

Diabetes and breast cancer among women with BRCA1 and BRCA2 mutations

BACKGROUND:

Hyperinsulinemia and the metabolic syndrome are both risk factors for breast cancer. It is not clear if diabetes is associated with the risk of breast cancer in women with a BRCA1 or BRCA2 mutation.

METHODS:

The authors reviewed the medical histories of 6052 women with a BRCA1 or BRCA2 mutation, half of whom had been diagnosed with breast cancer. They estimated the odds ratio for breast cancer, given a self‐report of diabetes. They then estimated the hazard ratio for a new diagnosis of diabetes associated with a history of breast cancer.

RESULTS:

There was no excess of diabetes in the period before the diagnosis of breast cancer, compared with controls with no diagnosis of breast cancer. The risk of diabetes was doubled among BRCA carriers in the 15‐year period after the diagnosis of breast cancer (relative risk, 2.0; 95% confidence interval [CI], 1.4‐2.8; P = .0001), compared with carriers without cancer. The risk was particularly high for women with a body mass index (BMI) >25.0 kg/m² (odds ratio, 5.8; 95% CI, 4.0‐8.6; P = .0001).

CONCLUSIONS:

After a diagnosis of breast cancer, women with a BRCA1 or BRCA2 mutation face a 2‐fold increase in the risk of diabetes, which is exacerbated by a high BMI. Cancer 2011. © 2010 American Cancer Society.