EMMPRIN、HER-2蛋白表达与胃癌侵袭转移的关系

目的: 探讨细胞外基质金属蛋白酶诱导因子(EMMPRIN)、人表皮生长因子受体2(HER-2/neu)蛋白表达与人胃癌侵袭转移的关系, 以及2种蛋白表达之间的关系.方法: 应用量子点免疫荧光组织化学技术检测人胃癌组织芯片150芯(包括70例胃癌组织和5例正常胃黏膜组织)中EMMPRIN和HER2的蛋白表达, 并分析他们与临床病理特征的相关性.结果: 胃癌和正常胃黏膜组织中的EMMPRIN阳性表达率分别为72.86%和20.00%, 差异有显著性( P = 0.029). 在胃癌组织中HER-2蛋白的阳性率为47.14%(33/70), 高于正常胃黏膜组织, 但差异无显著性( P = 0.063).EMMPRIN、HER-2蛋白表达与胃癌患者年龄、性别、分化程度、肿瘤的浸润深度以及临床TNM分期之间差异均无显著性( P>0.05),仅与淋巴结转移显著相关( P<0.05). 在70例胃癌组织中EMMPRIN与HER-2蛋白表达之间呈显著正相关( r = 0.383, P = 0.001).结论: EMMPRIN与HER-2/neu可能协同促进了胃癌的淋巴结转移.     

大肠癌EGFR、HER-2、VEGF表达特点及其对分子靶向治疗的指导意义

目的:探讨大肠癌中表皮生长因子受体(EGFR)、人类表皮生长因子受体-2(HER-2)和血管内皮生长因子(VEGF)的表达特点及其对大肠癌分子靶向治疗的指导意义.方法:随机选取2005-05/2009-03中国人民解放军空军总医院普通外科行根治性手术的大肠癌患者78例. 应用免疫组织化学法检测大肠癌肿瘤组织中EGFR、HER-2、VEGF的表达, 并结合其临床病理特点进行回顾性分析.结果:EGF R、HE R-2、VEGF在大肠癌中的阳性表达率依次为38 . 5%( 30 / 78 ) 、53.8%(42/78)、41.0%(32/78). 三者的表达与性别、年龄、肿瘤部位、分化类型无关, 而与肿瘤的大小、侵袭深度和转移密切相关.EGFR与HER-2及VEGF, HER-2与VEGF在大肠癌肿瘤组织中表达呈正相关(r = 0.421,0.484, 0.469, P = 0.019, 0.012, 0.016).结论:EGFR、HER-2、VEGF的表达参与大肠癌的生长、侵袭和转移过程. 三者的联合检测可作为判断大肠癌预后、筛选高危转移患者的有效指标, 同时, 也可用于指导大肠癌的靶向药物治疗.     

ADAM17、HER-2和VEGF在结直肠癌组织中表达及临床意义

目的探讨去整合素-金属蛋白酶(ADAM17)原癌基因人表皮生长因子受体(HER)-2及血管内皮生长因子(VEGF)在结直肠癌中的表达及相关性。方法采用免疫组化的方法检测41例结直肠癌组织标本及其对应的癌旁组织中ADAM17、HER-2及VEGF的表达水平,并分析其表达水平与临床病理参数之间的关系。结果 ADAM17、HER-2及VEGF在结直肠癌组织中的阳性表达率显著高于其癌旁组织(P0. 05),ADAM17、HER-2、VEGF的表达均分别与是否有淋巴结转移和临床分期相关(P0. 05),三个因子之间存在相关。结论 ADAM17、HER-2、VEGF在结直肠癌发生发展中关系密切,联合检测可作为筛选高危转移患者的指标,并可作为判断预后,指导化疗靶向药物选择的重要依据。     

胃癌组织中HER-2的表达变化及意义

目的观察胃癌组织中表皮生长因子受体2（HER-2）的表达变化,并探讨其意义。方法采用免疫组化EnVision法检测45例胃癌组织（胃癌组）和20例正常胃组织（对照组）中的HER-2。结果胃癌组17例、对照组1例HER-2表达阳性,两组HER-2阳性表达率比较,P〈0．05。HER-2表达与胃癌淋巴结转移有关（P〈0．05）。结论胃癌组织中HER-2表达增高,HER-2可能与胃癌的淋巴结转移有关。     

ARTN、VEGF蛋白在胃癌组织中的表达及意义

目的 探讨Artemin(ARTN)、血管内皮生长因子(VEGF)蛋白在胃癌组织中的表达和意义.方法 采用免疫组化方法,检测60例胃癌患者的癌组织及48例胃癌患者的癌旁良性组织中ARTN、VEGF蛋白的表达,并分析二者与胃癌患者临床病理特征和预后的关系.结果 ARTN、VEGF蛋白在癌旁良性组织中的阳性表达率分别为14.6％、12.5％,在胃癌组织中的阳性表达率分别为78.3％、70.0％.胃癌组织中的ARTN、VEGF蛋白阳性表达率均明显高于癌旁良性组织(P均＜0.01).ARTN蛋白表达与胃癌患者的肿瘤浸润程度、TNM分期及淋巴结转移有密切关系(P均＜0.05),且ARTN蛋白与VEGF蛋白表达呈正相关(r=0.131,P＜0.01).结论 胃癌组织中的ARTN蛋白表达与肿瘤的侵袭转移有密切关系,与VEGF蛋白表达呈正相关,可作为临床评价胃癌进展和患者预后的指标之一.     

大肠癌组织人表皮生长因子受体2表达对患者预后的影响

目的探讨大肠癌组织人表皮生长因子受体2(HER-2/neu)表达对患者预后的影响。方法大肠癌患者140例,均行根治性手术。采用免疫组织化学或荧光原位杂交法(FISH)检测大肠癌组织HER-2/neu。比较HER-2/neu阳性组、阴性者的临床病理资料、5年生存率,分析术后生存的危险因素。结果 HER-2/neu阳性、阴性者性别、年龄、分化程度、肿瘤部位、T分期比较P均>0.05;N分期、TNM临床分期比较,P均<0.05。HER-2/neu阳性者5年生存率为54.7%,阴性者为74.8%,P=0.03。HER-2/neu是影响大肠癌患者术后5年生存率的独立危险因素(RR=1.068,95%CI:1.009~1.129,P=0.02)。结论 HER-2/neu可作为结肠癌预后评估的指标之一。     

环氧合酶-2和血管内皮生长因子-C的表达与胃癌淋巴结转移的关系

目的 探讨胃癌组织中环氧合酶-2(COX-2)和血管内皮生长因子-C(VEGF-C)的表达及其与淋巴管生成和淋巴结转移之间的关系.方法 采用免疫组化S-P法检测85例胃癌组织和20例正常胃组织中的COX-2、VEGF-C及微淋巴管密度(MLD),并结合临床病理特征进行分析.结果 COX-2、VEGF-C在胃癌组织中的阳性表达率为77.6%、72.9%,COX-2在胃癌组织中的表达与VEGF-C、临床分期、MLD、淋巴结转移有关,差异有统计学意义(P＜0.05),COX-2、VEGF-C与胃癌组织学分型、肿瘤大小、患者性别及年龄均无明显关系(P＞0.05).结论 COX-2、VEGF-C在胃癌组织中高表达,COX-2与VEGF-C、MLD及淋巴结转移呈正相关,COX-2可能通过上调VEGF-C表达参与胃癌微淋巴管生成而发生淋巴结转移.     

高迁移率族蛋白B1和血管内皮生长因子在老年直肠癌中的表达及其与预后的相关性

目的探讨老年直肠癌组织中高迁移率族蛋白(HMG)B1和血管内皮生长因子(VEGF)表达与直肠癌临床病理特征及直肠癌患者预后的相关性。方法选取该院2012年12月至2014年12月手术治疗的122例老年直肠癌患者,应用免疫组化法检测122例直肠癌组织中HMGB1和VEGF的表达,分析其与直肠癌临床病理特征的关系,二者在直肠癌中表达的相关性及其与老年直肠癌患者预后的相关性。采用KaplanMeier法作生存分析,分析HMGB1和VEGF的表达与患者预后生存期的关系。结果 HMGB1和VEGF在直肠癌组织中的阳性表达率分别为66.39%和59.02%,HMGB1的阳性表达率与TNM分期、淋巴结转移和浸润深度有关(P0.05),而与性别、分化程度和远处转移无关(P0.05)。VEGF阳性表达率与TNM分期、淋巴结转移、远处转移和浸润深度有关(P0.05),而与患者的性别、分化程度无关(P0.05)。HMGB1和VEGF在直肠癌中的阳性表达率呈显著正相关(r=0.576,P0.01)。Kaplan-Meier生存分析结果显示,HMGB1和VEGF表达阳性患者的中位生存期显著低于表达阴性者(P0.05)。结论直肠癌中HMGB1和VEGF的表达与直肠癌临床病理特征和预后密切相关,联合检测HMGB1和VEGF对判断结老年直肠癌的预后具有一定的指导意义。     

血管内皮生长因子在胃癌中表达及其预后意义

目的研究血管内皮生长因子(VEGF)在胃癌组织中表达的临床意义.方法应用抗 VEGF 多克隆抗体的免疫组织化学方法,观察 VEGF 在胃癌组织中的表达,分析 VEGF 表达与不同监床病理因素及预后之间关系.结果 128例胃癌 VEGF 阳性表达率为64.1%;Ⅲ、Ⅳ期病人 VEGF 阳性表达率明显高于Ⅰ期患者(P<0.05);VEGF 阳性表达率与肿瘤的生长方式、浸润深度及淋巴线转移关系之间有显著统计学意义,肿瘤呈浸润型生长(71.8%)或浸及浆膜者(73.5%)明显大于膨胀型生长(52.0%)或无浆膜浸润者(53.3%)(P<0.025),淋巴结转移阳性肿瘤(75.0%)明显大于无淋巴结转移者(50.0%)(P<0.05);此外,在86例术后随访患者中,VEGF 阳性表达肿瘤患者的术后5年生存率明显低于 VEGF 阴性表达肿瘤患者(P<0.05).     

HER-2/neu基因在非小细胞肺癌中的表达及其临床意义

目的探讨HER-2/neu基因在非小细胞肺癌中的表达及其临床意义。方法应用免疫组化法检测90份非小细胞肺癌组织及20份正常肺组织HER-2/neu基因的表达。结果 HER-2/neu基因在90份非小细胞肺癌组织中过度表达率为32.2%(29/90),20份正常肺组织中无过度表达。非小细胞肺癌的HER-2/neu基因的过度表达与年龄、性别、分化程度均无相关性(P均>0.05),与肿瘤的病理类型、淋巴结转移、临床分期、生存期相关(P均<0.05)。结论检测非小细胞肺癌组织中HER-2/neu基因的表达,有助于判断其预后,也为抗HER-2/neu基因的分子靶向治疗应用于非小细胞肺癌中提供理论依据。     

Clinical significance of HER-2/neu expression in colon cancer]

BACKGROUND/AIMS: The HER-2/neu protein is involved in normal cell proliferation and tissue growth because it is extensively homologous and related to epidermal growth factor receptor. As a prognostic marker, HER-2/neu is used to forecast the clinical course and poor outcome in breast cancer. As a predictive marker, HER-2/neu is used to predict the therapeutic response to adjuvant chemotherapy and endocrine therapy in breast cancer. In this study, we investigated the relationships between clinical and pathologic characteristics of tumor and prognosis according to the HER-2/neu expression in colon cancer. This study was conducted for the future introduction of Herceptin therapy for colon cancer patients. METHODS: Overexpression of HER-2/neu was examined by semiquantitative standardized immunohistochemical staining kit in 88 patients with colon cancer. The patients underwent curative surgery at the Kangbuk Samsung Hospital. RESULTS: Overexpression of HER-2/neu was detected in 11 (12.5%) of 88 patients. Tumors with positive HER-2/neu staining showed a tendency for higher rates of nodal metastasis and poor mean survival (1,646 +/- 269 vs 2,631 +/- 141 days) and 5-year survival (65.5% vs 78.9%). CONCLUSIONS: Tumors with positive HER-2/neu staining showed a tendency for higher rates for nodal metastasis and poor clinical survival rate.     

HER-2/neu Amplification Is an Independent Prognostic Factor in Gastric Cancer

The HER-2/neu protein is intimately involved with normal cell proliferation and tissue growth and is extensively homologous and related to the epidermal growth factor receptor. HER-2/neu protein expression has been most intensively studied in the context of breast carcinoma, in which its amplification and overexpression correlate with the overall course of disease, and with a poor prognosis, and constitute a predictive factor of poor response to chemotherapy and endocrine therapy. In this study, we investigated the relationship between the expression of HER-2/neu and the clinicopathological characteristics of tumors, including survival. This study was performed with a view toward the future introduction of Herceptin therapy for gastric cancer patients. HER-2/neu overexpression and gene amplification was examined with semiquantitative standardized immunohistochemical staining, chromogenic in situ hybridization (CISH), and fluorescence in situ hybridization (FISH) in 182 gastric cancer patients who underwent curative surgery at the Kangbuk Samsung Hospital. Twenty-nine (15.9%) of 182 patients expressed the HER-2/neu protein by immunohistochemistry. HER-2/neu gene amplification was detected in seven patients by CISH and FISH. Intestinal-type cancers exhibited higher rates of HER-2/neu amplification than did diffuse-type cancers (P < 0.05). Tumors with HER-2/neu amplification were associated with poor mean survival rates (922 vs 3243 days) and 5-year survival rates (21.4% vs 63.0%; P < 0.05). Age, TNM stage, and amplification of HER-2/neu were found to be independently related to survival by multivariate analysis. HER-2/neu amplification may constitute an independent prognostic factor in gastric cancer patients, and patients exhibiting HER-2/neu amplification might constitute potential candidates for new adjuvant therapies which involve the use of humanized monoclonal antibodies.     

荧光原位杂交法对胃癌组织HER-2基因状态的检测

目的:比较荧光原位杂交(FISH)法与免疫组织化学(IHC)染色法检测胃癌组织HER-2基因状态的一致性.方法:选择本课题组前期IHC染色法检测775例胃腺癌标本中HER-2蛋白表达为(2+)及(3+)的病例,应用FISH法对HER-2基因扩增情况进行验证.结果:FISH结果显示,86例HER(3+)标本中,60例存在...     

Relationship between expression of NADPH oxidase 2 and invasion and prognosis of human gastric cancer

AIM: To assess the expression and prognostic value of nicotinamide adenine dinucleotide phosphate oxidase 2(NOX2) in gastric cancer, and its correlation with vascular endothelial growth factor(VEGF) and epidermal growth factor receptor(EGFR).METHODS: Tumor and adjacent tissues were obtained from 123 patients who underwent radical surgery for gastric cancer at Renmin Hospital of Wuhan University from 2008-2009. The expression of NOX2, VEGF, EGFR and CD68 in tumor tissues was detected by immunohistochemistry. The expression of NOX2 in gastric cancer and adjacent tissues was detected by Western blot analysis. Spearman's correlation was performed to elucidate the relationship of NOX2 with VEGF and EGFR. The Kaplan-Meier method was used to calculate survival time, and the log-rank test was used to evaluate differences in survival. Cox‘s proportional hazards regression model was applied in a stepwise manner to analyze the independent prognostic factors.RESULTS: NOX2 exhibited positive expression in 47.2%(58/123) of the gastric cancer tissues. Western blot analysis revealed that NOX2 was up-regulated in tumor tissues compared to the adjacent tissue [39.0%(48/123)]. Immunohistochemistry staining revealed that CD68, which is a specific marker of macrophages, and NOX expression presented a similar localization and staining intensity. The expression of NOX2 was positively correlated with that of VEGF and EGFR. Comparison of the 5-year survival rates of the NOX2 positive and NOX2 negative groups showed that the NOX2 positive group presented a poor prognosis.CONCLUSION: NOX2 positively correlates with the levels of VEGF and EGFR. NOX2 may be used as a new biomarker and a potential therapeutic target for gastric cancer.     

Correlation of immunohistochemically detected HER-2/neu (c-erbB-2) with histological stage and perineural invasion in pancreatic cancer

BACKGROUND/AIMS: HER-2/neu (c-erbB-2) oncoprotein is a transmembrane glycoprotein and may function as a growth factor being involved in the regulation of cell growth and cell transformation. c-erbB-2 was correlated with established outcome factors in pancreatic cancer. METHODOLOGY: We performed an analysis of 100 patients with pancreatic cancer using an immunoperoxidase technique on formalin-fixed, paraffin-embedded tissue samples in order to determine HER-2/neu oncoprotein expression along with stage and perineural involvement. RESULTS: HER-2/neu oncoprotein was expressed in the tumors of 21 patients (21%). CONCLUSIONS: Histologic stage, and perineural invasion did not correlate with HER-2/neu oncoprotein.     

VEGF与bcl-2在胃癌组织中的表达及其临床病理学意义

目的探讨VEGF与bcl-2在胃癌组织中的表达和2者之间的相关性及其临床病理学意义。方法应用免疫组化SABC法对93例胃癌组织及其周围正常胃组织中VEGF与bcl-2的表达进行研究。结果VEGF与bcl-2在胃癌组织和正常胃组织的阳性表达率均有非常显著的差异(P<0·01),VEGF与bcl-2的表达呈显著的关联性;2者的表达与胃癌的转移行为有关,而与肿瘤分型和分化程度无关。结论VEGF与bcl-2基因协同作用,共同促进胃癌的发生、发展和转移。     

p53、PTEN和VEGF在胃癌组织中的表达及意义

目的探讨p53、PTEN、VEGF表达在胃癌发生、发展中的作用及其相关影响因素。方法采用免疫组织化学法检测80份胃癌组织中p53、PTEN、VEGF表达,并分析其与胃癌临床病理特征的关系。结果 p53、PTEN、VEGF在胃癌组织中的阳性表达率依次为55%(44/80)、92.5%(74/80)、52.5%(42/80);胃癌组织中p53、VEGF表达阳性率明显高于对照组,P<0.01。三者表达与性别、年龄、肿瘤分化程度、浸润情况、淋巴结转移等均无明显相关性;任意两个指标之间相关性亦不显著。结论 p53、VEGF对胃癌的诊断有一定价值;p53、VEGF、PTEN对胃癌肿瘤分化、浸润和转移等的诊断价值不大,各指标间的相关性不显著。     

Molecular targeting to treat gastric cancer

Trastuzumab that targets human epidermal growth factor receptor 2 (HER2) protein is the only approved molecular targeting agent for treating gastric cancer in Japan and the outcomes have been favorable. However, trastuzumab is effective for only 10% to 20% of the population with gastric cancer that expresses HER2 protein. Molecular targeting therapy with bevacizumab against vascular endothelial growth factors (VEGF) and with cetuximab and panitumumab against the epidermal growth factors pathway that have been approved for treating colorectal cancer are not considered effective for treating gastric cancer according to several clinical trials. However, ramucirumab that targets VEGF receptor-2 prolonged overall survival in a large phase III clinical trial and it might be an effective molecular targeting therapy for gastric cancer. The significance of molecular targeting therapy for gastric cancer remains controversial. A large-scale randomized clinical trial of novel molecular targeting agents with which to treat gastric cancer is needed.     

HER-2/neu overexpression is an independent prognostic factor in colorectal cancer

Background and aims The HER-2/neu protein is intimately involved with normal cell proliferation and tissue growth, as it is extensively homologous and is related to the epidermal growth factor receptor. This phenomenon has been most intensively studied in the context of breast carcinoma, in which its amplification and overexpression correlate with the overall course of disease and poor prognoses, and also constitute a predictive factor of poor response to chemotherapy and endocrine therapy. In this study, we investigated the relationships between the expression of HER-2/neu and the clinicopathological characteristics of colorectal cancer, including survival. This study was performed with a view toward the future introduction of Herceptin therapy for colorectal cancer patients. Patients and methods HER-2/neu overexpression and gene amplification were examined via semiquantitative standardized immunohistochemical staining and fluorescence in situ hybridization (FISH) in 137 colorectal cancer patients who underwent curative surgery at the Kangbuk Samsung Hospital. Results Sixty-five (47.4%) out of 137 patients were determined by immunohistochemistry to have overexpressed HER-2/neu protein. HER-2/neu gene amplification was detected in two patients by FISH. Tumors with HER-2/neu overexpression showed higher postoperative recurrence rate (39.3% vs 14.6%, p=0.013). Tumors with HER-2/neu overexpression were associated with poor 3-year (70.8% vs 83.7%) and 5-year survival rates (55.1% vs 78.3%, p<0.05). Advanced TNM stage, postoperative recurrence, and overexpression of HER-2/neu were found to be independently related to survival by multivariate analysis. Conclusion HER-2/neu overexpression may constitute an independent prognostic factor in colorectal cancer patients, and patients exhibiting HER-2/neu overexpression might constitute potential candidates for a new adjuvant therapy which involves the use of humanized monoclonal antibodies.