HER-2基因Ile655Val多态性与结直肠癌易感性分析

目的 探讨HER-2原癌基因Ile655Val多态性与结直肠癌易感性的相关性,及其在自然人群中的分布频率.方法 应用病例对照研究,对浙江省嘉善县292例结直肠癌患者和842名健康对照者采用聚合酶链反应-限制性片段长度多态性方法检测HER-2基因密码子655基因型.结果 结直肠癌组HER-2基因Ile/Val+Val/Val基因型频率(25.34%)和Val等位基因频率(13.36%)均显著高于对照组(18.41%和9.74%)(P<0.05).与Ile/lie基因型携带者相比,Ile/Val+Val/Val基因型携带者患结直肠癌的风险增加(OR=1.54,95%CI:1.11～2.14).HER-2基因多态性与吸烟、饮酒的交互作用OR值分别为1.43(95%CI:0.88～2.30)和1.29(95%CI:0.73～2.29).结论 HER-2基因Ile655Val多态性与结直肠癌易感性相关,但是这种多态性与吸烟、饮酒在结直肠癌发生中不存在交互作用.     

HER-2基因Ile655Val多态性与结直肠癌易感性分析

目的 探讨HER-2原癌基因Ile655Val多态性与结直肠癌易感性的相关性,及其在自然人群中的分布频率.方法 应用病例对照研究,对浙江省嘉善县292例结直肠癌患者和842名健康对照者采用聚合酶链反应-限制性片段长度多态性方法检测HER-2基因密码子655基因型.结果 结直肠癌组HER-2基因Ile/Val+Val/Val基因型频率(25.34%)和Val等位基因频率(13.36%)均显著高于对照组(18.41%和9.74%)(P<0.05).与Ile/lie基因型携带者相比,Ile/Val+Val/Val基因型携带者患结直肠癌的风险增加(OR=1.54,95%CI:1.11～2.14).HER-2基因多态性与吸烟、饮酒的交互作用OR值分别为1.43(95%CI:0.88～2.30)和1.29(95%CI:0.73～2.29).结论 HER-2基因Ile655Val多态性与结直肠癌易感性相关,但是这种多态性与吸烟、饮酒在结直肠癌发生中不存在交互作用.     

HER-2基因Ile655Val多态性与结直肠癌易感性分析

目的 探讨HER-2原癌基因Ile655Val多态性与结直肠癌易感性的相关性,及其在自然人群中的分布频率.方法 应用病例对照研究,对浙江省嘉善县292例结直肠癌患者和842名健康对照者采用聚合酶链反应-限制性片段长度多态性方法检测HER-2基因密码子655基因型.结果 结直肠癌组HER-2基因Ile/Val+Val/Val基因型频率(25.34%)和Val等位基因频率(13.36%)均显著高于对照组(18.41%和9.74%)(P<0.05).与Ile/lie基因型携带者相比,Ile/Val+Val/Val基因型携带者患结直肠癌的风险增加(OR=1.54,95%CI:1.11～2.14).HER-2基因多态性与吸烟、饮酒的交互作用OR值分别为1.43(95%CI:0.88～2.30)和1.29(95%CI:0.73～2.29).结论 HER-2基因Ile655Val多态性与结直肠癌易感性相关,但是这种多态性与吸烟、饮酒在结直肠癌发生中不存在交互作用.     

HER-2基因Ile655Val多态性与结直肠癌易感性分析

目的 探讨HER-2原癌基因Ile655Val多态性与结直肠癌易感性的相关性,及其在自然人群中的分布频率.方法 应用病例对照研究,对浙江省嘉善县292例结直肠癌患者和842名健康对照者采用聚合酶链反应-限制性片段长度多态性方法检测HER-2基因密码子655基因型.结果 结直肠癌组HER-2基因Ile/Val+Val/Val基因型频率(25.34%)和Val等位基因频率(13.36%)均显著高于对照组(18.41%和9.74%)(P<0.05).与Ile/lie基因型携带者相比,Ile/Val+Val/Val基因型携带者患结直肠癌的风险增加(OR=1.54,95%CI:1.11～2.14).HER-2基因多态性与吸烟、饮酒的交互作用OR值分别为1.43(95%CI:0.88～2.30)和1.29(95%CI:0.73～2.29).结论 HER-2基因Ile655Val多态性与结直肠癌易感性相关,但是这种多态性与吸烟、饮酒在结直肠癌发生中不存在交互作用.     

HER-2基因Ile655Val多态性与结直肠癌易感性分析

目的 探讨HER-2原癌基因Ile655Val多态性与结直肠癌易感性的相关性,及其在自然人群中的分布频率.方法 应用病例对照研究,对浙江省嘉善县292例结直肠癌患者和842名健康对照者采用聚合酶链反应-限制性片段长度多态性方法检测HER-2基因密码子655基因型.结果 结直肠癌组HER-2基因Ile/Val+Val/Val基因型频率(25.34%)和Val等位基因频率(13.36%)均显著高于对照组(18.41%和9.74%)(P<0.05).与Ile/lie基因型携带者相比,Ile/Val+Val/Val基因型携带者患结直肠癌的风险增加(OR=1.54,95%CI:1.11～2.14).HER-2基因多态性与吸烟、饮酒的交互作用OR值分别为1.43(95%CI:0.88～2.30)和1.29(95%CI:0.73～2.29).结论 HER-2基因Ile655Val多态性与结直肠癌易感性相关,但是这种多态性与吸烟、饮酒在结直肠癌发生中不存在交互作用.     

HER-2基因Ile655Val多态性与结直肠癌易感性分析

目的 探讨HER-2原癌基因Ile655Val多态性与结直肠癌易感性的相关性,及其在自然人群中的分布频率.方法 应用病例对照研究,对浙江省嘉善县292例结直肠癌患者和842名健康对照者采用聚合酶链反应-限制性片段长度多态性方法检测HER-2基因密码子655基因型.结果 结直肠癌组HER-2基因Ile/Val+Val/Val基因型频率(25.34%)和Val等位基因频率(13.36%)均显著高于对照组(18.41%和9.74%)(P<0.05).与Ile/lie基因型携带者相比,Ile/Val+Val/Val基因型携带者患结直肠癌的风险增加(OR=1.54,95%CI:1.11～2.14).HER-2基因多态性与吸烟、饮酒的交互作用OR值分别为1.43(95%CI:0.88～2.30)和1.29(95%CI:0.73～2.29).结论 HER-2基因Ile655Val多态性与结直肠癌易感性相关,但是这种多态性与吸烟、饮酒在结直肠癌发生中不存在交互作用.     

HER-2基因Ile655Val多态性与结直肠癌易感性分析

目的 探讨HER-2原癌基因Ile655Val多态性与结直肠癌易感性的相关性,及其在自然人群中的分布频率.方法 应用病例对照研究,对浙江省嘉善县292例结直肠癌患者和842名健康对照者采用聚合酶链反应-限制性片段长度多态性方法检测HER-2基因密码子655基因型.结果 结直肠癌组HER-2基因Ile/Val+Val/Val基因型频率(25.34%)和Val等位基因频率(13.36%)均显著高于对照组(18.41%和9.74%)(P<0.05).与Ile/lie基因型携带者相比,Ile/Val+Val/Val基因型携带者患结直肠癌的风险增加(OR=1.54,95%CI:1.11～2.14).HER-2基因多态性与吸烟、饮酒的交互作用OR值分别为1.43(95%CI:0.88～2.30)和1.29(95%CI:0.73～2.29).结论 HER-2基因Ile655Val多态性与结直肠癌易感性相关,但是这种多态性与吸烟、饮酒在结直肠癌发生中不存在交互作用.     

HER-2基因Ile655Val多态性与结直肠癌易感性分析

目的 探讨HER-2原癌基因Ile655Val多态性与结直肠癌易感性的相关性,及其在自然人群中的分布频率.方法 应用病例对照研究,对浙江省嘉善县292例结直肠癌患者和842名健康对照者采用聚合酶链反应-限制性片段长度多态性方法检测HER-2基因密码子655基因型.结果 结直肠癌组HER-2基因Ile/Val+Val/Val基因型频率(25.34%)和Val等位基因频率(13.36%)均显著高于对照组(18.41%和9.74%)(P<0.05).与Ile/lie基因型携带者相比,Ile/Val+Val/Val基因型携带者患结直肠癌的风险增加(OR=1.54,95%CI:1.11～2.14).HER-2基因多态性与吸烟、饮酒的交互作用OR值分别为1.43(95%CI:0.88～2.30)和1.29(95%CI:0.73～2.29).结论 HER-2基因Ile655Val多态性与结直肠癌易感性相关,但是这种多态性与吸烟、饮酒在结直肠癌发生中不存在交互作用.     

HER-2基因Ile655Val多态性与结直肠癌易感性分析

目的 探讨HER-2原癌基因Ile655Val多态性与结直肠癌易感性的相关性,及其在自然人群中的分布频率.方法 应用病例对照研究,对浙江省嘉善县292例结直肠癌患者和842名健康对照者采用聚合酶链反应-限制性片段长度多态性方法检测HER-2基因密码子655基因型.结果 结直肠癌组HER-2基因Ile/Val+Val/Val基因型频率(25.34%)和Val等位基因频率(13.36%)均显著高于对照组(18.41%和9.74%)(P<0.05).与Ile/lie基因型携带者相比,Ile/Val+Val/Val基因型携带者患结直肠癌的风险增加(OR=1.54,95%CI:1.11～2.14).HER-2基因多态性与吸烟、饮酒的交互作用OR值分别为1.43(95%CI:0.88～2.30)和1.29(95%CI:0.73～2.29).结论 HER-2基因Ile655Val多态性与结直肠癌易感性相关,但是这种多态性与吸烟、饮酒在结直肠癌发生中不存在交互作用.     

HER-2基因Ile655Val多态性与结直肠癌易感性分析

目的 探讨HER-2原癌基因Ile655Val多态性与结直肠癌易感性的相关性,及其在自然人群中的分布频率.方法 应用病例对照研究,对浙江省嘉善县292例结直肠癌患者和842名健康对照者采用聚合酶链反应-限制性片段长度多态性方法检测HER-2基因密码子655基因型.结果 结直肠癌组HER-2基因Ile/Val+Val/Val基因型频率(25.34%)和Val等位基因频率(13.36%)均显著高于对照组(18.41%和9.74%)(P<0.05).与Ile/lie基因型携带者相比,Ile/Val+Val/Val基因型携带者患结直肠癌的风险增加(OR=1.54,95%CI:1.11～2.14).HER-2基因多态性与吸烟、饮酒的交互作用OR值分别为1.43(95%CI:0.88～2.30)和1.29(95%CI:0.73～2.29).结论 HER-2基因Ile655Val多态性与结直肠癌易感性相关,但是这种多态性与吸烟、饮酒在结直肠癌发生中不存在交互作用.     

HER-2基因Ile655Val多态性与结直肠癌易感性分析

目的 探讨HER-2原癌基因Ile655Val多态性与结直肠癌易感性的相关性,及其在自然人群中的分布频率.方法 应用病例对照研究,对浙江省嘉善县292例结直肠癌患者和842名健康对照者采用聚合酶链反应-限制性片段长度多态性方法检测HER-2基因密码子655基因型.结果 结直肠癌组HER-2基因Ile/Val+Val/Val基因型频率(25.34%)和Val等位基因频率(13.36%)均显著高于对照组(18.41%和9.74%)(P<0.05).与Ile/lie基因型携带者相比,Ile/Val+Val/Val基因型携带者患结直肠癌的风险增加(OR=1.54,95%CI:1.11～2.14).HER-2基因多态性与吸烟、饮酒的交互作用OR值分别为1.43(95%CI:0.88～2.30)和1.29(95%CI:0.73～2.29).结论 HER-2基因Ile655Val多态性与结直肠癌易感性相关,但是这种多态性与吸烟、饮酒在结直肠癌发生中不存在交互作用.     

Allellic HER-2 codon 655 polymorphism and the influence of plasma HER-2 levels in breast cancer Egyptian female patients

Breast cancer is the most common type of cancer and the most common cause of cancer-related mortality among women worldwide. Alterations of human epidermal growth factor receptor-2 (HER-2) proto-oncogene have been associated with carcinogenesis and poor prognosis of breast cancers. HER-2 DNA amplification is suggested to be the principal mechanism of HER-2 protein activation. The aim of the study was to clarify the possible association between HER-2 gene polymorphism at codon 655, free plasma HER-2 level, and breast cancer risk. Eighty Egyptian female patients (40 with early breast cancer and 40 with locally advanced breast cancer) were tested for HER-2 genetic polymorphism at codon 655 by restriction fragment length polymorphism–polymerase chain reaction assay. Also, the plasma level of HER-2 was measured using enzyme-linked immunosorbent assay. There was significant increase in mutant G allele frequency among locally advanced group compared to the control group and this conferred 12-fold increased disease risk among the studied group. No significant association could be detected between early breast cancer and HER-2 gene polymorphism. There is a statistically significant increase in the mean plasma HER-2 level among locally advanced breast cancer patients in comparison to the control group suggesting that plasma HER-2 contributes to the development, the higher stage, and dissemination of breast cancer.     

FISH技术在乳腺癌HER-2基因检测中的应用

乳腺癌患者HER-2是否过度表达不仅能指导临床用药,更可以提示预后,在乳腺癌的诊治中起着至关重要的作用.而约25%-30%的浸润性乳腺癌和80%的乳腺导管内癌患者有HER-2基因扩增或蛋白过表达,检测HER-2的过度表达不仅能指导临床用药,还可以提示预后.因此找到一个能够准确检测HER-2状态的方法就显得更加重要.FISH法是一种检测HER-2基因扩增的有效的方法.可以检查分裂期细胞的核型、识别染色体数目、确定肿瘤细胞系的来源等.这种方法为我们今后根据HER-2的状态治疗乳腺癌以及判断预后提供了一个方便有效的途径.     

HER-2基因及蛋白的检测在乳腺癌临床诊断中的价值

目的探讨用免疫组化（immunohistochemistry,IHC）和显色原位杂交技术（chromogenic in situ hybridization,CISH）检测乳腺癌HER-2蛋白表达和基因扩增在临床病理诊断及分子靶向治疗中的应用及意义。方法用免疫组化（IHC）和显色原位杂交技术（CISH）检测60例乳腺癌石蜡包埋组织标本中HER-2蛋白的表达及基因扩增情况,比较两种方法的结果以及与临床病理的关系。结果 HER-2蛋白过表达与HER-2基因扩增之间密切相关。结论两者综合结果的判定对乳腺癌患者的临床治疗有明确的指导意义,可用于临床赫塞汀（Herceptin）分子靶向治疗病例的筛选。     

Estrogen receptor codon 594 and HER2 codon 655 polymorphisms and breast cancer risk

The estrogen receptor (ER) and the human epithelial growth factor receptor 2 (HER2) genes have been implicated in the development and prognosis of breast cancer. Several genetic polymorphic sites in these genes have been identified and associated with the risk of breast cancer. We have investigated the association between the estrogen receptor codon 594 (ACA to ACG) and HER2 codon 655 (ATC to GTC) polymorphisms and breast cancer risk. Genomic DNA from breast cancer patients and control subjects was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). When allelic frequencies of the ER codon 594 and HER2 codon 655 gene were compared, no significant differences were observed between the patient and control groups. (P = 0.063, OR = 1.55, 95% CI = 0.25-9.41 and P = 0.949, OR = 1.01, 95% CI = 0.55-1.88, respectively). In conclusion, our results support the view that both the ER codon 594 and HER2 codon 655 polymorphisms are not associated with increased risk of breast cancer.     

Her2 genotype and breast cancer progression in Korean women

The amplification and overexpression of Her2 proto-oncogene have been found to be associated with the development and progression of human breast cancer. A polymorphic valine allele at codon 655 of the Her2 gene (Her2(V655)) was suggested by some authors to be a susceptible genetic factor for the development of breast cancer. The Her2 polymorphism at codon 655 was investigated in 304 Korean women including 177 patients with breast cancer. The association between Her2 genotype and Her2 protein overexpression was also examined in breast cancers by immunohistochemistry. Her2(V655) was not associated with a significant breast cancer risk (odds ratio (OR), 1.792; 95% confidence interval (CI), 0.459-6.991). The frequency of homozygous or heterozygous valine allele increased in stage 2 patients (OR, 1.67; 95% CI, 0.67-4.19), and patients in stages 3 and 4 (OR, 3.36; 95% CI, 0.85-13.42) compared to patients in stage 0. However, an association between the presence of the valine allele and the overexpression of Her2 protein could not be demonstrated. These results suggest that Her2 polymorphism at codon 655 is not associated with the development of breast cancer in Korean women. However, there is a possibility that the valine allele at codon 655 might be related to increased risk of breast cancer progression.     

人乳腺癌MCF-7细胞在不同HER-2水平miRNAs表达谱检测

目的：通过对比观察人乳腺癌细胞MCF-7和MCF-7/HER-2中微小RNA( miRNAs)的差异性表达,初步筛选出与HER-2表达相关的miRNAs表达谱。方法培养人乳腺癌细胞MCF-7和MCF-7/HER-2,利用miRNA芯片技术检测两株细胞中miR-NAs的表达。结果利用miRNA微阵列,筛选获得217种与HER-2相关的miRNAs,较正常MCF-7细胞上调的miRNAs有123个,下调的有94个。在差异有显著性的miRNAs中,hsa-miR-141和hsa-miR-1299的靶基因有多种生物学功能。结论获得人乳腺癌MCF-7细胞在不同HER-2水平miRNAs的差异表达谱,为进一步分析HER-2在乳腺癌中的作用奠定基础。     

筛选并初步分析不同 HER-2水平的人乳腺癌 BT474细胞内miRNAs差异性表达

目的：检测两株人乳腺癌细胞BT474和BT474/siRNA HER-2微小RNA( miRNAs)的表达,初步筛选与HER-2相关差异性表达的miRNAs。方法用干扰RNA技术沉默人乳腺癌细胞株BT474中HER-2基因的表达,利用miRNA芯片技术比较两株细胞BT474和BT474/siRNA HER-2内miRNAs的表达。结果差异倍数>2且P<0．05,与HER-2相关的miRNAs有338个;其中110个miRNAs上调,228个miRNAs下调。结论用miRNA芯片技术可以筛选人乳腺癌BT474细胞在不同HER-2水平差异性表达的miRNAs,进一步分析筛选,有望在乳腺癌中寻找到与HER-2相关的miRNAs。     

Quantitative real-time polymerase chain reaction is an alternative method for the detection of HER-2 amplification in formalin-fixed paraffin-embedded breast cancer samples

Fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) are the most common methods that are used to quantify HER-2 gene and protein levels, respectively, in human breast cancer. However, due to bad sample quality, some samples are unable to be subjected to a FISH assay. We evaluated 71 formalin-fixed paraffin-embedded (FFPE) breast carcinoma specimens by quantitative real-time polymerase chain reaction (qPCR), IHC, and FISH. We also performed qPCR and FISH assays on delayed formalin-fixed (DDF) samples. The qPCR results were in complete concordance with the results of IHC and FISH. In regards to the DDF samples, the HER-2 fluorescent signal seemed decayed compared with that of the DDF samples after 1 h. However, the qPCR method still works well up to 12 hours. Our results indicated that qPCR was obviously superior to FISH in cases that were not fixed in a reasonable amount of time. However, qPCR can be an alternative method by which to perform HER2 amplification assays in breast cancer.     

Immunohistochemical COX-2 overexpression correlates with HER-2/neu overexpression in invasive breast carcinomas: a pilot study

Cyclooxygenase-2 (COX-2) is a prostaglandin synthase that catalyzes the synthesis of prostaglandin G2 and H2. It has been shown that COX-2 plays an important role in tumorigenesis of different tumor types and it is thought to take part in breast carcinogenesis. In the present study, we aimed to investigate the relationship of immunohistochemical COX-2 expression with clinicopathological parameters, including HER-2/neu overexpression in invasive breast carcinoma (IBC).Our study population comprised 10 normal breasts, 25 ductal carcinomas in situ (DCIS), and 51 invasive breast carcinomas. Immunohistochemical overexpressions of COX-2 and HER-2/neu were investigated in sections of formalin-fixed, paraffin-embedded blocks by 3 observers.In normal breast, DCIS and IBC, the COX-2 overexpression rate was 0%, 84%, and 58.8%, respectively. In IBC, COX-2 overexpression had a significant relationship with HER-2/neu overexpression (p = 0.026) and a high histological grade (p = 0.026). COX-2 expression in both DCIS (n = 25) and IBC (n = 51) was significantly higher than in normal breast tissue (p < 0.0001). In addition, the COX-2 expression rate was significantly higher in DCIS than in IBC (p = 0.042).Our results indicated that COX-2 overexpression correlates with aggressive phenotypic features, such as HER-2/neu overexpression and high histological grade in IBC. Increased expression of COX-2 in both DCIS and IBC in comparison to normal breast could indicate a role in breast carcinogenesis. COX-2 overexpression may provide a clinically useful biomarker for estimating tumor aggressiveness.