乙酰肝素酶基因表达与胃癌临床病理特点的关系

目的探讨乙酰肝素酶基因(HPAmRNA)在胃癌中的表达及其与临床病理因素之间的相互关系。方法选用43例胃癌组织和10例癌旁正常胃组织,用逆转录聚合酶链反应(RTPCR)检测标本中HPAmRNA的表达,并结合患者临床病理指标进行分析。结果43例胃癌中,29例HPAmRNA表达阳性,其阳性率显著高于癌旁正常胃组织(P=0.013)。HPAmRNA的表达与TNM分期、有无浆膜浸润、淋巴结转移、远处转移以及与肿瘤大小有相关性(P<0.05);与患者年龄、性别、肿瘤所在部位、肿瘤的Borrmann分型、组织学类型、分化程度、腹膜转移和肝转移无相关性(P>0.05)。结论HPAmRNA阳性表达的胃癌有较高的侵袭转移性,HPA可能是胃癌侵袭转移中的一个重要酶,可能与胃癌的淋巴结转移有关。     

FGFR2 gene amplification and clinicopathological features in gastric cancer

Background:

Frequency of FGFR2 amplification, its clinicopathological features, and the results of high-throughput screening assays in a large cohort of gastric clinical samples remain largely unclear.

Methods:

Drug sensitivity to a fibroblast growth factor receptor (FGFR) inhibitor was evaluated in vitro. The gene amplification of the FGFRs in formalin-fixed, paraffin-embedded (FFPE) gastric cancer tissues was determined by a real-time PCR-based copy number assay and fluorescence in situ hybridisation (FISH).

Results:

FGFR2 amplification confers hypersensitivity to FGFR inhibitor in gastric cancer cell lines. The copy number assay revealed that 4.1% (11 out of 267) of the gastric cancers harboured FGFR2 amplification. No amplification of the three other family members (FGFR1, 3 and 4) was detected. A FISH analysis was performed on 7 cases among 11 FGFR2-amplified cases and showed that 6 of these 7 cases were highly amplified, while the remaining 1 had a relatively low grade of amplification. Although the difference was not significant, patients with FGFR2 amplification tended to exhibit a shorter overall survival period.

Conclusion:

FGFR2 amplification was observed in 4.1% of gastric cancers and our established PCR-based copy number assay could be a powerful tool for detecting FGFR2 amplification using FFPE samples. Our results strongly encourage the development of FGFR-targeted therapy for gastric cancers with FGFR2 amplification.     

子宫内膜癌组织HER2表达水平与患者临床病理特征的关系探讨

目的 探讨子宫内膜癌组织中人表皮生长因子受体2(HER2)的表达水平及其临床意义.方法 选取84例子宫内膜癌组织标本为病例组,30例正常子宫内膜组织标本为对照组,采用免疫组化染色方法检测两组标本中HER2蛋白的表达水平,分析HER2蛋白表达水平与子宫内膜癌患者临床病理特征的关系.结果 病例组组织标本中HER2蛋白的阳性表达率为55.95％,高于对照组的26.67％,差异有统计学意义(P﹥0.05);肌层浸润深度﹥1/2、Ⅲ期和Ⅳ期、低分化、发生淋巴结转移、肿瘤累及宫颈组织的子宫内膜癌患者子宫内膜癌组织中HER2蛋白阳性表达率高于肌层浸润深度≤1/2、Ⅰ期和Ⅱ期、高分化和中分化、未发生淋巴结转移、肿瘤未累及宫颈组织的子宫内膜癌患者,差异均有统计学意义(P﹤0.05).结论 子宫内膜癌组织中HER2蛋白的表达上调,并且与肿瘤浸润深度、临床分期、分化程度、淋巴结转移及是否累及宫颈组织有关.     

胃癌组织中成纤维细胞激活蛋白的表达及其与临床病理特征的关系

目的探讨胃癌组织中成纤维细胞激活蛋白(FAP)的表达与临床病理特征和预后的关系。方法选取2009年4月至2011年3月间江苏省中国人民解放军第82医院行手术治疗的121例胃癌患者的胃癌组织标本为研究对象,采用免疫组化染色检测癌变组织及距离癌变组织超过5cm处正常组织中FAP的表达情况,分析其与临床病理特征的关系。对患者进行5年随访,分析FAP表达与患者预后生存的关系。结果 121例胃癌病理组织中FAP表达阳性者为109例(90.1%),FAP阳性表达细胞数平均为(32.99±13.24)个,FAP在癌旁正常组织中的表达均为阴性。胃癌组织中FAP表达与患者肿块直径、分化程度、TNM分期和淋巴转移有关,差异均有统计学意义(均P<0.05),与患者年龄、性别和是否吸烟无关。胃癌组织FAP高表达患者的平均生存时间及95%CI为35.29(27.82,42.77)个月,而低表达患者平均生存时间及95%CI为44.15(38.84,49.46)个月,两者比较,差异有统计学意义(P<0.05)。结论胃癌组织中FAP呈高表达,与胃癌的生长、进展和预后有关。     

乳腺癌组织人端粒酶逆转录酶表达及其临床病理意义

目的：分析乳腺浸润性导管癌中人端粒酶逆转录酶（hTERT）的蛋白表达与肿瘤的临床分期、组织学分级、转移及患者预后的关系.方法：采用免疫组化SLAB法,检测67例乳腺浸润性导管癌石蜡包埋组织中hTERT的蛋白表达.结果：67例乳腺浸润性导管癌中强阳性者44例,弱阳性者23例.hTERT蛋白主要定位于癌细胞胞质,少部分细胞核也有表达.本组乳腺癌分期和分级越高,hTERT蛋白表达的强阳性率越高,P值分别为0.002 8和0.010 2.hTERT强阳性组转移率为63.6%（28/44）,弱阳性组转移率为30.4%（7/23）,两者差异有统计学意义,P=0.0000.hTERT强阳性组3年生存率为69.2%（27/39）,hTERT弱阳性组3年生存率为95.7%（22/23）,两者差异有统计学意义,P=0.0000.结论：hTERT的蛋白表达可能与乳腺浸润性导管癌的分化和转移有关,可以作为判断乳腺癌患者预后的指标之一.     

乳腺癌组织人端粒酶逆转录酶表达及其临床病理意义

目的:分析乳腺浸润性导管癌中人端粒酶逆转录酶(hTERT)的蛋白表达与肿瘤的临床分期、组织学分级、转移及患者预后的关系。方法:采用免疫组化SLAB法,检测67例乳腺浸润性导管癌石蜡包埋组织中hTERT的蛋白表达。结果:67例乳腺浸润性导管癌中强阳性者44例,弱阳性者23例。hTERT蛋白主要定位于癌细胞胞质,少部分细胞核也有表达。本组乳腺癌分期和分级越高,hTERT蛋白表达的强阳性率越高,P值分别为0.002 8和0.010 2。hTERT强阳性组转移率为63.6%(28/44),弱阳性组转移率为30.4%(7/23),两者差异有统计学意义,P=0.000 0。hTERT强阳性组3年生存率为69.2%(27/39),hTERT弱阳性组3年生存率为95.7%(22/23),两者差异有统计学意义,P=0.000 0。结论:hTERT的蛋白表达可能与乳腺浸润性导管癌的分化和转移有关,可以作为判断乳腺癌患者预后的指标之一。     

Adjuvant FAM2 in resectable gastric cancer

In spite of the improvements in surgical techniques and intensive care, no important benefit in the prognosis of patients with gastric carcinoma has been attained in the last twenty years. Different adjuvant treatment protocols have been proposed in an attempt to improve upon the results obtained with surgery only. In western countries, the FAM chemotherapeutic regimen is one on the most widely used for the treatment of advanced gastric carcinoma. In 1982 the G.I. GROUP of the EORTC proposed a modification (FAM2) to the original FAM as an adjuvant treatment in a controlled clinical study for gastric carcinoma. It is still too early to determine any therapeutic advantages of FAM2 in this protocol. Although the FAM2 regimen is fairly well tolerated, there is some toxicity which, however, seems to be slightly higher than in the regular FAM. It remains to be seen if this is a reasonable price to pay for still unknown therapeutic advantages. In view of the scarcity of available data in this field and the conflicting results which have emerged so far, the results of our study are awaited with great interest.     

RFT2在胃癌中的表达及其临床意义

目的 探讨胃癌组织中核黄素转运蛋白2(riboflavin transporter-2,RFT2)表达及其与胃癌临床病理参数之间的关系.方法 取胃癌石蜡包埋组织标本及癌旁胃黏膜组织标本各60例,用免疫组织化学方法检测癌组织RFT2蛋白表达水平.结果 RFT2蛋白在胃癌组织中的表达水平低于癌旁正常胃黏膜组织(P＜0.05).胃癌组织中RFT2蛋白表达水平在胃癌的分化程度、TNM分期、Lauren组织学分型方面差异有统计学意义(均P＜0.05),在患者性别、民族、年龄、有无淋巴结转移、肿瘤大小方面差异无统计学意义(均P＞0.05).结论 RFT2蛋白表达在人胃癌组织中表达显著下降,其表达与肿瘤组织分化程度及TNM分期密切相关.     

血清COX-2在乳腺癌中的表达及与临床病理特征关系的研究

目的 利用酶联免疫吸附试验(ELISA)方法 检测乳腺癌患者血清环氧化酶-2(cyclooxygenase-2,COX-2)并探讨其与临床病理特征之间的关系.方法 随机抽取2009年9月至2010年9月柳州工人医院普通外科收治的乳腺癌患者65例,乳腺良性病变患者30例,正常人25例.采用ELISA法检测3组入选者血清COX-2水平,并作统计学分析,探讨COX-2与各项临床病理特征之间的关系.结果 血清COX-2在乳腺癌中均有表达.在65例乳腺癌中,血COX-2含量临床分期Ⅲ+Ⅳ期组比0+Ⅰ+Ⅱ期组高;有腋窝淋巴结转移者比无腋窝淋巴结转移者高;ER、PR阴性组较阳性组高;p21阳性组较阴性组高.结论 ①COX-2表达与乳腺癌发生、发展有关;②COX-2含量与患者TNM分期、腋淋巴结转移情况、ER、PR、p21有关.检测COX-2有助于评价乳腺癌患者的临床及预后.     

HER2-positive gastric cancer

Human epidermal growth factor receptor 2 (HER2) is involved in the pathogenesis and poor outcomes of several types of cancer, including advanced gastric and gastroesophageal junction cancer. Molecular-targeted drugs, such as trastuzumab, which prolong overall survival and progression-free survival in HER2-positive breast cancer, may also be beneficial in patients with HER2-positive gastric cancer. Several studies have examined this possibility, such as the Trastuzumab for Gastric Cancer trial. In this context, the first part of this review provides an update on our knowledge of HER2 in breast and gastric cancer, including the detection and prognostic relevance of HER2 in gastric cancer. The second part of the review discusses the results of pivotal clinical trials that examined the potential for using trastuzumab to treat this disease. This section also summarizes the trials that have been conducted or that are underway to determine the optimal uses of trastuzumab in gastric cancer, including its use as monotherapy and continuation beyond disease progression. The final section discusses the future prospects of other anti-HER2 drugs, including lapatinib, trastuzumab emtansine, and pertuzumab, for the treatment of HER2-positive gastric cancer. The introduction of trastuzumab led to the establishment of a new disease entity, “HER2-positive gastric cancer,” similar to HER2-positive breast cancer. It is expected that more anti-HER2 drugs will be developed and introduced into clinical practice to treat HER2-positive cancers, including gastric cancer.     

Correlation between Claudin-18 expression and clinicopathological features and prognosis in patients with gastric cancer

BackgroundTo investigate the correlation between Claudin-18 expression and the clinicopathological features and prognosis of gastric cancer.MethodsA total of 63 patients who underwent gastric cancer surgery from December 2012 to June 2013 were recruited as the research participants. The clinicopathological data and prognostic information of the participants were collected, and expression levels of Claudin-18 in gastric cancer and adjacent tissues were detected by immunohistochemical (IHC) staining. The correlation between Claudin-18 expression and clinicopathological features of gastric cancer patients was analyzed. The Cox regression model was used to analyze the risk factors associated with the prognosis of gastric cancer patients.ResultsThe expression of Claudin-18 was positive in 35 (55.6%) of the participants’ gastric cancer tissues, which was significantly lower than that in the adjacent tissues (51 tissues/81.0%), and the difference was statistically significant (P=0.002). In addition, the IHC staining score of Claudin-18 expression in gastric cancer tissues (1.49±1.69), was significantly lower than that in the adjacent tissues (4.61±1.81), and the difference was statistically significant (P=0.016), The incidence of nerve invasion in patients with low expression of Claudin-18 was significantly higher than that in patients with high expression of Claudin-18 (P=0.038). In addition, univariate Cox regression analysis showed that nerve invasion, Claudin-18 staining score, tumor size, and positive count of lymph nodes were risk factors associated with the survival of gastric cancer patients. Multivariate Cox regression analysis showed that Claudin-18 staining score and tumor size were independent risk factors associated with the survival of gastric cancer patients. The overall survival (OS) of patients with low Claudin-18 staining score or larger tumor size was significantly reduced.ConclusionsThe low expression of Claudin-18 was closely related to nerve invasion in gastric cancer, which indicated the poor clinical prognosis of gastric cancer patients.     

HER2 expression in gastric and oesophageal cancer: a meta-analytic review

Background

Since the advent and the success of adjuvant medical therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the form of trastuzumab there has been increasing interest in the development of similar therapies in other solid organ malignancies including gastric cancer and oesophageal cancer. Over the years, multiple observational studies have been inconsistent. Several meta-analyses have been published looking at the association between HER2 and gastric cancer and oesophageal cancer. This review aims to summarize the meta-analytic evidence for the association between HER2 in gastric and oesophageal cancer.

Methods

A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane Library, Google Scholar, Science Direct, and Web of Science.

Results

Of the articles selected, only nine studies met full criteria. Six of them reviewed the role of HER2 in gastric cancer and the remaining three reviewed its role in oesophageal cancer.

Conclusions

The current evidence regarding the role of HER2 is unclear. However, it clearly plays a key role in the pathogenesis of gastric and oesophageal carcinomas. Targeted therapy towards this subgroup (despite variable frequency and association with survival) would offer a mortality benefit and improve survival.     

新疆地区不同民族胃癌患者HER2蛋白表达与临床病理学特征的关系

目的：利用新疆地区有利条件探究胃癌患者HER2/neu表达与民族及临床病理特征的关系。方法：随机选取2010年-2012年新疆维吾尔自治区人民医院收治的120例原发胃癌患者（胃食管交界处肿瘤33例,胃体部肿瘤35例,胃窦部肿瘤52例）,应用免疫组织化学（ immunohistochemistry,IHC）法检测胃癌患者的HER2/neu表达情况,应用新版《胃癌HER2检测指南》评分标准进行评分。数据分析采用SPSS 17.0统计软件。结果：120例胃癌组织中20例（16.7％）HER2/neu（﹢﹢﹢）,胃食管交界处肿瘤阳性率明显高于胃体/胃窦肿瘤（33.3％ vs 10.3％,P＝0.005）。肠型胃癌阳性率显著高于弥漫性/混合型胃癌（26.7％ vs 6.7％,P＝0.001）。汉族与少数民族（维族、哈族）之间HER2/neu蛋白阳性率（15.7％ vs 17.4％,P＝0.407）无明显差异。结论：肠型胃癌与胃食管交界处肿瘤是曲妥珠单抗联合化疗的主要适宜人群。     

Copine-8在胃癌组织中的表达与临床病理特征及预后的相关性

目的 探讨Copine-8(CPNE8)在胃癌组织中的表达与患者临床病理特征及预后的相关性。方法 收集2011年3月—2014年3月于仙桃职业学院附属医院行胃癌根治术并经过病理证实的胃癌组织标本144例,采用免疫组织化学分析CPNE8在胃癌及其配对的癌旁组织中的表达情况,并分析其与胃癌临床病理参数及预后的关系。结果 免疫组织化学结果表明,CPNE8阳性表达率在胃癌组织中较癌旁组织中明显升高(63.9% vs. 26.4%,χ²=36.450,P＜0.001);CPNE8的表达与胃癌患者的TNM分期及有无淋巴结转移密切相关(χ²=5.993,P=0.014;χ²=6.703,P=0.009)。Kaplan-Meier生存分析发现,CPNE8高表达患者总生存时间(OS)和无病生存时间(DFS)均明显短于CPNE8低表达患者(χ²=23.130,P＜0.001;χ²=21.570,P＜0.001)。TNM分期(HR=1.297,95% CI:1.018~1.652,P=0.036)、淋巴结转移(HR=1.340,95% CI:1.027~1.749,P=0.031)和CPNE8蛋白表达(HR=1.531,95% CI:1.208~1.940,P＜0.001)是影响胃癌患者OS的独立危险因素;TNM分期(HR=1.280,95% CI:1.028~1.593,P=0.027)和CPNE8蛋白表达(HR=6.010,95% CI:1.355~26.661,P=0.018)是影响胃癌患者DFS的独立危险因素。结论 CPNE8在胃癌组织中显著表达上调,并与患者恶性病理特征密切相关,CPNE8可成为胃癌患者预后评估的标志物之一。     

乳腺癌组织HSG和EGFR基因mRNA表达与临床病理因素相关性分析

目的:研究增殖抑制基因(HSG)和表皮生长因子受体(EGFR)在乳腺癌中的表达及其与临床病理因素的相关性。方法:应用实时荧光定量PCR及免疫组织化学方法来检测HSG和EGFR的mRNA在正常乳腺组织、乳腺纤维腺瘤和乳腺癌组织中的表达,以及它们在乳腺癌组织中表达的相关性。结果:乳腺癌组HSG mRNA表达水平和表达率显著低于正常乳腺组和乳腺腺瘤组,P<0.05。乳腺癌组EGFR mRNA表达水平和表达率显著高于正常乳腺组和乳腺腺瘤组,P=0.000。乳腺纤维腺瘤组织HSG和EGFR mRNA表达水平和阳性检出率与正常乳腺组织比较差异无统计学意义,P>0.05。乳腺癌组织HSG和EGFR的mRNA表达与淋巴结转移和病理组织学分级以及雌激素受体(ER)和HER-2有关,而与肿瘤类型、肿瘤大小、临床分期和年龄等无明显相关性,P>0.05。HSG与EGFR的mRNA表达负相关,r=-0.456,P=0.002。结论:乳腺癌组织HSG的mRNA表达随着分化程度的下降或淋巴结的转移或ER和HER-2阴性者,HSG的表达明显下降。而EGFR mRNA在组织分化程度低或ER和HER-2阳性的乳腺癌中的表达却明显增高。乳腺癌组织HSG的表达与EGFR的表达呈负相关。HSG与抑制乳腺癌组织的发生和淋巴转移正相关。     

肿瘤家族史与胃癌患者临床病理特征关系的研究

目的:探讨恶性肿瘤家族史（familial history of malignant neoplasm,MN-FH）对胃癌贡献比例及与临床病理特征之间的关系。方法:回顾我院2010年1月-2014年12月间收治的资料齐全的310例胃癌患者的临床病理资料,以有无肿瘤家族史分组,利用SPSS软件统计分析组间临床病理特征关系。结果:96例（31.0%）胃癌患者具有肿瘤家族史,其一级和二级亲属中共有64例（66.7%）具有消化道相关肿瘤,包括食管癌（19.8%）、胃癌（24.0%）、肝癌（6.3%）和结直肠癌（16.7%）。泌尿系肿瘤占12.5%,其他（包括甲状腺癌、乳腺癌、喉癌等）占20.8%。相关性分析显示有无肿瘤家族史在性别及肿瘤发生部位均没有差异（P＞0.05）。病理分型显示有MN-FH的胃癌患者以低分化、未分化多见,占60.4%(58/96),无MN-FH占12.6%(27/214),两组相比,P＜0.05。而在高、中分化腺癌类型上则相反,有MN-FH胃癌组占39.6%,无MN-FH胃癌组占87.3%,P＜0.05。胃癌临床分期显示有MN-FH多以Ⅲ、Ⅳ期为主（73.0%）,无MN-FH组以Ⅱ期为主（57.9%）,两组相比,P＜0.05,具有显著性差异。结论:我院超过1/3的胃癌患者具有阳性MN-FH。其中最常见的MN-FH是消化道肿瘤。MN-FH胃癌具有分化程度低,病理特征恶性程度高特点。对于有家族史人群定期体检非常重要,早诊和早治是提高生存率的关键。     

Targeting HER 2 and angiogenesis in gastric cancer

Gastric cancer is one of the most commonly diagnosed and the second leading cause of cancer death worldwide. Surgery combined with multimodal therapy remains the only curative therapy. However, local relapse or distant metastases occur in more than 50% of radically resected patients. Due to molecular therapies, targeting HER2 and angiogenesis, major advances in the treatment of gastric cancer could be achieved. Nevertheless, development of resistance to monoclonal antibodies, such as trastuzumab, is arising. Currently a number of promising new therapeutic are under investigation, combining chemotherapy with newly developed agents to overcome cancer resistance. In this review we report current clinical applications of targeted therapies and overview ongoing trials, investigating the use of monoclonal antibodies in (HER2 positive) gastric cancer.     

HE4在浆液性卵巢癌组织中的表达及与临床病理因素的关系

目的：探讨人附睾分泌蛋白4（ HE4）在浆液性卵巢癌组织中的表达及与临床病理因素之间的关系。方法应用免疫组化的方法检测HE4在140例浆液性卵巢癌组织中的表达情况及与临床病理因素的关系,并联合检测CA125在卵巢癌中的组织学表达情况,对比HE4与CA125的相关性。结果HE4和CA125在中低分化浆液性卵巢癌组织中的阳性表达率分别为89．76％和81．89％,在高分化者阳性率分别为46．61％和15．38％,中晚期卵巢癌者阳性率为92．44％和83．19％,早期卵巢癌者阳性率为47．62％和33．33％,有盆腔淋巴结转移者阳性率95．65％和84．35％,无盆腔淋巴结转移者40．00％和36．00％,有腹腔种植者阳性率90．00％和87．27％,无腹腔种植者70．00％和33．33％,卵巢癌合并腹水者阳性率89．76％和79．53％,无腹水者为46．15％和38．46％,另外,HE4和CA125在浆液性卵巢癌中的阳性表达率分别为86％和76％,差异均具有统计学意义（ P＜0．05）,两者在卵巢癌的阳性表达上存在相关性（P＜0．05）。 HE4和CA125的表达与卵巢癌患者是否绝经和产数无关,（P＞0．05）。结论 HE4在浆液性卵巢癌组织中的表达与FIGO分期、肿瘤分化程度、淋巴结有无转移、腹腔有无种植和是否合并腹水有关。     

Relationship between urokinase-type plasminogen receptor, interleukin-8 gene expression and clinicopathological features in gastric cancer

OBJECTIVE: The serine protease urokinase-type plasminogen (uPA) and its receptor (uPAR) appear to have a major function in tumor invasion and metastasis. Interleukin-8 (IL-8) acts as an angiogenic factor in solid cancer. The purpose of this study was to determine whether the expression of IL-8 and the uPAR gene correlates with clinicopathological parameters in human gastric carcinoma. METHODS: We examined the expression of uPAR mRNA and IL-8 mRNA using Northern blot analysis and RT-PCR in 35 gastric carcinomas and the surrounding normal mucosa. Macroscopic and histopathological tumor findings and survival rates were obtained from the patient records. RESULTS: uPAR and IL-8 mRNA expression levels were higher in most neoplasms compared to the corresponding normal mucosal tissue. A correlation between uPAR and IL-8 expression in tumors was observed (r = 0.447, p < 0.01). uPAR mRNA expression in the tumors correlated well with lymph node metastasis (p < 0.02), and its stage (p < 0.01). The IL-8 MRNA expression in the tumors correlated with diffuse-type gastric cancer (p < 0.05). The survival rates of patients with tumors displaying high uPAR expression levels were significantly lower (p < 0.04) than those of patients without uPAR expression, but patients with IL-8 expression only showed a tendency to a lower survival rate. CONCLUSION: These results suggest that uPAR and IL-8 may be important prognostic factors in human gastric carcinomas.