HER-2基因和MMP-2基因在结直肠癌中的表达和临床意义

目的:探讨人表皮生长因子受体-2(HER-2) 和基质金属蛋白酶-2(MMP-2) 在结直肠癌中的表达及其临床意义.方法:采用抗生蛋白链霉素-生物素标记法(SP) 免疫组化检测法 ,用HER-2 抗体、MMP-2抗体标记 64 例结直肠腺癌组织标本,并以大肠腺瘤15例及远癌正常大肠组织12例作对照,检测HER-2和MMP-2.结果: HER-2 及MMP-2在远癌组织中阳性率低于腺瘤性息肉组及腺癌组的表达,有统计学意义(P<0.05),腺瘤样息肉组与腺癌组表达率无统计学意义(P＞0.05).在结直肠癌病例中MMP-2 、HER-2 表达与结直肠癌患者性别、年龄、肿瘤分化程度、肿瘤浸润层次无关 (P>0.05) ,而与Ducks分期、有无转移淋巴结相关,C和D期结直肠癌患者切片中MMP-2 、HER-2表达率明显高于A和B期的患者 (P<0.05),有淋巴结转移的患者表达率明显高于无淋巴转移患者(P<0.05).HER-2 与MMP-2 表达存在显著正相关(r=0.303).结论: MMP-2 、HER-2 在正常组织、腺瘤性息肉及腺癌中的表达逐步上调,MMP-2 和HER-2在结直肠癌组织中表达明显升高,可能促进了大肠癌的转移、进展.MMP-2 、HER-2基因可能在结直肠癌的演进中起协同作用.     

EGFR在结直肠癌组织中的表达及其临床意义

目的：检测表皮生长因子受体（epidermal growth factor receptor,EGFR）在结直肠癌组织中的表达情况,分析其表达水平与各种主要临床病理学预后因子及长期生存的关系。方法：选取解放军307医院和301医院第二附属医院64例结直肠癌患者的石腊包埋肿瘤标本,以免疫组化方法检测结直肠癌肿瘤标本中EGFR的表达。通过单因素分析和多因素分析判断EGFR表达与临床病理学指标之间的关系;通过多因素分析（COX模型）判断EGFR表达水平与患者总生存期的关系。结果：所有患者肿瘤组织EGFR的阳性表达率为69%。T3期肿瘤EGFR阳性表达明显多于T1和T2期（P〈0.05）,淋巴结转移阳性者EGFR阳性表达明显多于无转移者（P〈0.05）,有远处转移者EGFR阳性表达明显多于无远处转移者（P〈0.05）;EGFR表达与患者性别、年龄、肿瘤原发部位、肿瘤大小、肿瘤分化程度等均无明显相关性。EGFR表达水平与患者总生存期无明显相关。结论：结直肠癌组织EGFR的表达与肿瘤TNM分期相关,与患者总生存期无明显相关。     

EGFR在结直肠癌组织中表达的意义

结直肠癌（carcinoma of colon and rectum,CRC）是最常见的恶性肿瘤之一,全球发病率有逐年上升的趋势。CRC的临床分期、组织学分级等常用指标并不能完全反映出其生物学行为及预后情况。因此,寻找对CRC诊断、治疗及预后有判断意义的指标,一直     

SPNS2在结直肠癌组织中的表达及其临床意义

  目的  探讨鞘氨醇-1-磷酸转运体2（spinster homolog 2,SPNS2）在结直肠癌组织中的表达及其临床意义。  方法  选取2010年1月至2013年6月于安徽省立医院经结直肠癌手术切除的133例患者的结直肠癌和癌旁正常组织标本,采用免疫组织化学法检测SPNS2蛋白的表达。另收集2018年2月至2018年6月的29例结直肠癌患者的癌组织和癌旁正常组织标本行RT-qPCR检测。采用χ2检验分析SPNS2在结直肠癌组织中的表达及与患者临床病理特征的关系。采用单因素和多因素分析SPNS2在结直肠癌组织中的表达情况与患者预后的关系。  结果  免疫组织化学法结果显示SPNS2在结直肠癌组织中的表达较癌旁正常组织高（81.20% vs. 22.60%,χ2=69.136,P＜0.001）。RT-qPCR结果显示SPNS2 mRNA在结直肠癌组织中的表达水平显著高于其对应的癌旁正常组织（t=3.974,P＜0.001）。SPNS2蛋白过表达与肿瘤分化程度、淋巴结转移数、肿瘤大小和浸润深度密切相关,差异具有统计学意义（P＜0.001）。SPNS2阴性患者的生存期明显优于阳性患者（χ2=13.080,P＜0.001）。单因素分析和Cox多因素分析表明,SPNS2异常表达会影响结直肠癌患者总生存率（overall survival,OS）,是患者预后的独立影响因素（P＜0.05）。  结论  SPNS2在结直肠癌组织中的阳性表达与结直肠肿瘤的发生发展有关,SPNS2作为一种新型结直肠肿瘤标记物,在临床上可作为评估患者预后、监测术后肿瘤侵袭转移的指标及诊疗新靶点。      

BCAP31在结直肠癌组织中的表达及其临床意义

目的:研究结直肠癌组织中BCAP31的表达情况及其与临床病理特征的关系。方法:利用GEPIA数据库和HPA数据库分析BCAP31在结直肠癌中的表达情况,UALCAN数据库分析BCAP31在结直肠癌中的表达及与结直肠癌临床病理特征的关系,在临床样本中用实时荧光定量PCR法（real-time fluorescence quantitative polymerase chain reaction,RT-qPCR）和免疫印迹法（western blot,WB）检测BCAP31在结直肠癌和癌旁组织中mRNA和蛋白的表达情况,卡方检验分析BCAP31 mRNA表达与临床病理特征的相关性。结果:与癌旁组织相比,BCAP31在结直肠癌中高表达(P<0.05),临床相关性分析其表达与淋巴结转移（P<0.05）和TNM分期有关(P<0.05),而与患者的年龄、性别、肿瘤部位、肿瘤分级、T分期和M分期无明显相关性(P>0.05)。结论:BCAP31在结直肠癌中高表达,且与肿瘤的淋巴结转移和TNM分期有关。BCAP31可作为结直肠癌治疗诊断的分子标志物。     

EGFR与HER-2在不同分子类型乳腺癌中的表达及其相关性分析

目的：探讨EGFR和HER-2在不同分子类型乳腺癌组织中的表达及其相关性。方法：回顾性分析2015年1月—2020年3月在邯郸市中心医院行手术治疗的乳腺癌患者资料650例(其中浸润性导管癌600例,浸润性小叶癌50例)及乳腺纤维腺瘤30例,应用免疫组织化学(IHC)方法对手术切除标本进行EGFR和HER-2蛋白表达检测,采用χ²检验及Spearman相关分析对数据进行统计学分析。结果：EGFR在乳腺浸润性导管癌中表达阳性率为48.7%,显著高于浸润性小叶癌(24.0%)及纤维腺瘤(16.7%)(P<0.01)。HER-2在乳腺浸润性导管癌中表达阳性率为27.8%,显著高于浸润性小叶癌(8.0%)及纤维腺瘤(6.7%)(P=0.002)。乳腺浸润性导管癌与浸润性小叶癌中,EGFR阳性率与HER-2评分等级呈正相关(r=1.000,P<0.05),且EGFR阳性率与HER-2阳性表达呈正相关(r=1.000,P<0.05)。EGFR阳性率在HER-2过表达型与三阴型乳腺癌组织中显著高于Luminal A型和Luminal B型,且Luminal B中HER-2阳性显著高于HER-2阴性亚型(P<0.001)。结论：EGFR、HER-2阳性率在乳腺浸润性导管癌显著升高,且EGFR阳性率与HER-2的评分等级及阳性表达率均呈正相关,EGFR在HER-2过表达型与三阴型乳腺癌组织中显著升高,为进一步研究HER-2阳性乳腺癌及三阴型乳腺癌的靶向药物治疗提供线索及理论依据。     

抗HER2治疗在转移性结直肠癌中的研究进展

结直肠癌(Colorectal cancer, CRC)是世界第三大常见癌症和第二大癌症相关死亡原因,严重威胁人类生命健康。尽管接受早期诊断和治疗,仍有相当部分结直肠癌患者因发生转移而预后较差。针对结直肠癌分子多样性的研究不但可指导预后,对患者个体化管理亦有重要参考意义。人表皮生长因子受体2(Human epidermal growth factor receptor-2,HER2)在乳腺癌、胃癌等多种恶性肿瘤中表达,抗HER2治疗能有效改善HER2阳性晚期乳腺癌、胃癌患者的预后。HER2作为转移性结直肠癌(metastatic colorectal cancer, mCRC)新兴的生物标志物近年来也备受关注。本文就目前HER2阳性mCRC的诊疗现状研究进展做一综述,以期为临床诊断、药物选择等提供参考。     

ERβ蛋白和COX-2蛋白在结直肠癌中的表达及临床意义

目的:探讨雌激素受体β(ERβ)和环氧化酶-2(COX-2)在结直肠癌中的表达及其临床意义。方法:采用免疫组化法检测ERβ、COX-2在62例结直肠腺癌组织标本中的表达,以其中大肠腺瘤13例及远癌正常大肠组织10例作对照。结果:ERβ及COX-2在远癌组织中阳性率低于腺瘤性息肉组及腺癌组的表达,其中远癌组织组与腺癌组有统计学差异(P<0.05),腺瘤性息肉组与腺癌组表达率无统计学差异(P>0.05)。在结直肠癌病例中ERβ、COX-2表达与结直肠癌患者性别、肿瘤分化程度、肿瘤浸润层次无关(P>0.05),而与Dukes分期、有无转移淋巴结相关。结论:ERβ、COX-2在正常组织、腺瘤性息肉及腺癌中的表达逐步上调,ERβ和COX-2在结直肠癌组织中表达明显升高,可能促进了大肠癌的转移、进展。ERβ、COX-2蛋白在结直肠癌的演进中起着协同作用。     

直肠癌和癌旁组织表皮生长因子受体的表达及其临床意义

1　材料与方法1.1　标本选取西安医科大学一附院 1992年 1月至 1993年12月间 53例直肠癌根治手术标本作为研究对象 ,所有病例术前均未做过任何化疗或放疗。其中男性 2 7例 ,女性 2 6例 ,年龄最大 76岁 ,最小 18岁 ,平均 50 .8岁。在 53例癌组织蜡块中 ,有 4 5例含有癌旁组织 (距癌组织小于 2 的粘膜组织 )。 15例正常直肠粘膜作为正常对照 ,53例中有 4 0例获完整随访资料 ,随访率为75 5%。1.2　主要试剂与方法兔抗人ＥＧＦＲ多克隆抗体 (ＳＡＮＴＡＣＲＵＺＵＳＡ)、ＳＰ免疫组化试剂盒 (ＺＹＭＥＤＵＳＡ)均购自北京市中山试剂公司。所有…     

MMP-2和p53表达在结直肠癌组织中的表达及其临床意义

目的探讨人结直肠癌组织中基质金属蛋白酶-2（MMP-2）和p53表达与其临床病理特征的关系。方法采用免疫组化EliVisionTM plus法,检测40例结直肠癌、20例结直肠腺瘤和20例正常结直肠组织中MMP-2和p53蛋白表达水平。结果40例结直肠癌组织中MMP-2和p53阳性表达率分别为80．0％（32／40）和82．5％（33／40）,明显高于正常结直肠组织、结直肠腺瘤组织中的阳性率（均为0、30．0％）。MMP-2和p53在结直肠癌中的表达与患者年龄、性别、肿瘤大小、肿瘤发生部位均无相关性（P〉0．05）,与组织学分化程度呈负相关,分化程度越差,蛋白阳性表达率越高,有淋巴结转移组蛋白阳性表达率明显高于无淋巴结转移组（P〈0．05）,与TNM分期呈正相关（P〈0．05）。MMP-2表达与肿瘤浸润深度有关（P〈0．05）,有远处转移组MMP-2蛋白阳性表达率明显高于无远处转移组（P〈0．05）,p53表达与肿瘤浸润深度以及远处转移均无相关性（P〉0．05）。结直肠癌组织中MMP-2表达与p53蛋白表达呈正相关（γs’=0．3742,P=0．0069）。结论MMP-2表达与结直肠癌淋巴结侵袭转移有关,p53基因突变后MMP-2表达增强。联合检测MMP-2和p53在结直肠癌中的表达对评估结直肠癌病情有一定意义。     

Association of Human Epidermal Growth Factor Receptor-2 Expression and Clinicopathological Findings in Patients with Colorectal Cancer

Background: To determine the frequency of HER-2 overexpression in colorectal cancer (CRC) patients,and to explore the relationship between clinicopathological prognostic factors and their effects on survival,based on immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) analysis. Materials andMethods: The study included 80 patients with a histologically proven diagnosis of CRC that received adjuvantFOLFOX-4 chemotherapy at our department between March 2006 and September 2010. Patient data wereanalyzed retrospectively. Results: The median follow-up period and age of the patients were 24 months and59 years, respectively. In immunohistochemical staining, 3+ staining was found in 2 patients (2.5%) while 2+was in 13 (16%) . FISH for HER-2 was performed for all of these 15 patients; samples which were 3+ showedpositivity but the ones with 2+ were negative. There was no significant correlation between HER-2 expressionand age, gender, tumor localization, histological subtype, grade, lymphovascular and perineural invasion, orpTN stage (P>0.05), even when the patients with HER-2 overexpression were analyzed separately. There wasalso no significant relationship between progression-free survival (PFS) and overall survival (OS), and HER-2expression, gender, tumor localization, obstruction-perforation, bleeding, histological type, grade, lymphovascularand perineural invasion, or pT staging (P>0.05); however, there was a significant relationship between lymphnode involvement, and PFS and OS (P<0.05). Conclusions: Evaluation of HER-2 overexpression in a morecomprehensive, multi-center, prospective trial with standardized methods will be an appropriate approach.     

Association of Human Epidermal Growth Factor Receptor 2 with Radiotherapy Resistance in Patients with T1N0M0 Breast Cancer

Purpose

Preclinical studies have shown that human epidermal growth factor receptor 2 (HER2) status is associated with resistance to radiotherapy (RT). In this study, we evaluated the overall survival of a T1N0M0 breast cancer cohort in Korea according to the use of RT and the HER2 status.

Methods

We analyzed data collected from 11,552 patients with invasive breast cancer who were enrolled in the Korean Breast Cancer Society Registration Program between 1999 and 2007. Data on the TNM stage, estrogen receptor status, progesterone receptor status, HER2 status, operation method, and the use of RT were analyzed.

Results

The median follow-up period was 51 months. A significant improvement in overall survival after RT was observed only in the HER2(-) group. In this group, the 10-year overall survival rate was 95.5% for patients who did not receive RT and 96.3% for patients who received RT (p=0.037). In contrast, in the HER2(+) group, RT was not associated with a survival benefit (p=0.887). Multivariate analysis showed that RT was significantly associated with a reduction in mortality in the HER2(-) group (hazard ratio, 0.738; 95% confidence interval, 0.549-0.993; p=0.045).

Conclusion

We found that postoperative RT was not associated with a survival benefit in HER2(+) breast cancer patients, suggesting that HER2(+) breast cancers could be RT resistant.     

肝癌衍生生长因子在乳腺癌中的表达及其临床意义

目的探讨肝癌衍生生长因子（HDGF）在乳腺癌中的表达及其临床意义。方法应用免疫组织化学SP法检测113例乳腺癌和32例乳腺良性增生性病变中HDGF表达及乳腺癌中人类表皮生长因子受体2（HER-2）、雌激素受体（ER）和孕激素受体（PR）的表达。比较HDGF与ER、PR、HER-2表达以及其与临床病理因素之间的关系。采用Kaplan-Meier法对不同HDGF表达水平乳腺癌患者进行单因素生存分析,利用Cox模型进行多因素生存分析。结果腺癌组织中HDGF高表达率显著高于乳腺良性增生性病变组织（P<0.01）。HDGF表达与患者的年龄、绝经状况及病理类型、ER、PR表达无明显相关性(P>0.05）,但与患者瘤体大小,淋巴结转移,远处转移、临床分期及HER-2表达显著相关(P<0.01或0.05)。5年生存率HDGF低表达组明显高于高表达组（P<0.01）。HDGF是乳腺癌预后的一项重要因素(RR=1.263,P<0.05)。结论HDGF高表达与乳腺癌的预后不良有关,可作为一个新的判断乳腺癌预后的参考指标。     

Human Epidermal Growth Factor Receptor Family‐Targeted Therapies in the Treatment of HER2‐Overexpressing Breast Cancer

Breast cancer characterized by overexpression of human epidermal growth factor receptor 2 (HER2) has been associated with more aggressive disease progression and a poorer prognosis. Although an improved understanding of breast cancer pathogenesis and the role of HER2 signaling has resulted in significant survival improvements in the past 20 years, resistance to HER2‐targeted therapy remains a concern. A number of strategies to prevent or overcome resistance to HER2‐targeted therapy in breast cancer are being evaluated. This article provides a comprehensive review of (a) the role of HER2 signaling in breast cancer pathogenesis, (b) potential receptor and downstream therapeutic targets in breast cancer to overcome resistance to HER2‐targeted therapy, and (c) clinical trials evaluating agents targeting one or more members of the HER family and/or downstream pathways for the treatment of breast cancer, with a focus on metastatic disease.     

Lack of Prognostic Value of Human Epidermal Growth Factor-Like Receptor 2 Status in Inflammatory Breast Cancer (IBC): a Meta-analysis

Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer which is more likely to be her-2/neu amplified. While the her-2/neu status has been utilised to predict prognosis, the published data are inconsistent.The present meta-analysis was conducted to determine whether the her-2/neu status predicts outcomes. Paperswere selected from the PubMed database based on defined inclusion and exclusion criteria. Parameters such astotal patients, follow-up time and outcome statistics (i.e. overall survival (OS), relapse-free survival (RFS) werecollected. The analysis included 6 studies with 2,838 IBC patients. The summary hazards ratio (HR) estimatingthe association of OS with HER-2-positive disease was 0.96 (95% confidence interval (95%CI: 0.85-1.10)), withsimilar findings for RFS (HR=0.81, 95%CI: 0.61-1.09). No obvious statistical heterogeneity was detected. Thismeta-analysis suggests that HER-2-positive status is not an independent adverse prognostic factor for survivalamong IBC patient cases.     

Safety and Tolerability of Docetaxel,Cyclophosphamide, and Trastuzumab Compared to Standard Trastuzumab-Based Chemotherapy Regimens for Early-Stage Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer

Purpose

We evaluated the tolerability and cardiac safety of docetaxel, cyclophosphamide, and trastuzumab (TCyH) for the treatment of early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer and compared to the standard trastuzumab-based chemotherapy regimens doxorubicin with cyclophosphamide followed by paclitaxel and trastuzumab (AC-TH) and docetaxel, carboplatin, and trastuzumab (TCaH).

Methods

We retrospectively reviewed early-stage, resectable, HER2-positive breast cancer patients treated with trastuzumab-based chemotherapy at a single comprehensive cancer center between 2004 and 2011. Patient characteristics, comorbidities, relative dose intensity (RDI) of each regimen, tolerability, and cardiac toxicity were evaluated.

Results

One hundred seventy-seven patients were included in the study (AC-TH, n=114; TCaH, n=39; TCyH, n=24). TCyH was solely administered in the adjuvant setting, whereas two-thirds of the AC-TH and TCaH groups were administered postoperatively. Patients treated with TCyH tended to have a more significant underlying cardiac history, higher Charlson comorbidity index, and were of an earlier stage. All patients treated with TCyH received granulocyte colony stimulating factor primary prophylaxis. No febrile neutropenia or grade ≥3 hematologic toxicity was observed in the TCyH group as compared to the AC-TH and TCaH groups. There were no significant differences in the rates of early termination, hospitalization, dose reduction, or RDI between the regimens. The symptomatic congestive heart failure rate between AC-TH, TCaH, and TCyH groups was not significantly different (4.4% vs. 2.6% vs. 8.3%, respectively, p=0.57). There was also no significant difference in the rate of early trastuzumab termination between patients treated with each regimen.

Conclusion

TCyH is well tolerated and should be investigated as an alternative adjuvant chemotherapy option for patients who are not candidates for standard trastuzumab-containing regimens. Larger clinical trials are necessary to support the wider use of TCyH as an adjuvant regimen.     

Hormone Receptor and Human Epidermal Growth Factor Receptor 2 Detection in Invasive Breast Carcinoma: A Retrospective Study of 12,467 Patients From 19 Chinese Representative Clinical Centers

IntroductionWe evaluated the current status of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) detection in invasive breast carcinoma (IBC) in various laboratories across China.Materials and MethodsThe Breast Pathology Study Group of the Chinese Society of Pathologists collected HR and HER2 data from 12,467 IBC cases from 19 representative clinical centers in China. The data from every center were compared with the pooled data from the other centers.ResultsThe assessment of HR status showed that the overall positive estrogen receptor (ER) and progesterone receptor (PR) rates were 71.7% and 63.7% (range, 60.9%-87.9% and 43.9%-84.8%), respectively. The ER results in 3 centers and the PR results in 6 centers were outside the 99.5% confidence interval and were considered to be outliers (P < .0005). Of the 12,467 cases, 62.4% were ER⁺/PR⁺, 9.3% were ER⁺/PR⁻, 1.3% were ER⁻/PR⁺, and 27.0% were ER⁻/PR⁻. The assessment of HER2 status showed that the overall positive rate of HER2 (with a definition of immunohistochemistry [IHC] 3+ or IHC2+/ in situ hybridization-positive) was 24.7% (range, 13.7%-35.7%) in each center. Three centers were outside the 99.5% confidence interval and were considered to be outliers (P < .0005). The proportion of HER2 IHC3+ was 21.1%. The positive rates of HER2 gene amplification in IHC 0/1+, 2+, 3+ cases were 2.0%, 17.6%, and 85.9%, respectively.ConclusionsAs the largest study of HR and HER2 status in Chinese patients with IBC, the data from the present study have indicated that the overall rates of HR and HER2 were comparable to those reported in previous studies. However, the rates varied among the laboratories. Individual centers had not met the target values, and they need to improve the detection.     

表皮生长因子及其受体在大肠癌中的表达及其意义

目的通过检测表皮生长因子及其受体在大肠癌中的表达，探讨其在大肠癌中的意义。方法应用SP法免疫组化方法检测10例正常大肠黏膜、64例大肠癌组织中表皮生长因子及其受体的表达。结果正常大肠黏膜中表皮生长因子及其受体均为阴性表达，而其在大肠癌中的表达分别为51％和66％，与正常组比较有非常显著性差异（P〈0．01）；在大肠癌中表皮生长因子与其受体存在显著正相关性（P〈0．01）。结论表皮生长因子及其受体在大肠癌的发生发展过程中起着重要的作用。     

超声显像特征与乳腺癌组织中HER-2表达的关系研究

目的分析乳腺癌中超声显像特征与乳腺癌组织HER-2表达的关系。方法回顾性分析女性乳腺癌患者共84例,收集其术前检查的超声显像特征,并收集其病理结果中免疫组化法检测的HER-2表达的结果,分析超声显像特征与乳腺癌组织HER-2表达的关系。结果 84例女性乳腺癌患者中,其中HER-2表达为阴性的共21例,弱阳性共26例,阳性29例,强阳性的8例,其中低表达56. 0%,高表达44%,超声特征中乳腺癌的HER-2表达水平与肿瘤大小、内部钙化呈显著相关性(P <0. 05),而乳腺癌的HER-2表达水平与边缘情况、肿瘤形状、肿瘤纵横比、内部回声、后方回声衰减和血供分级没有显著的相关性(P> 0. 05)。结论超声特征中乳腺癌的HER-2表达水平与肿瘤大小和内部钙化具有密切的关系。