食管鳞状细胞癌中RNF113A的表达及临床病理意义

目的 探讨环指蛋白113A(ring finger protein 113A,RNF113A)在食管鳞状细胞癌(esophageal squamous cell carcinoma, ESCC)组织中的表达及临床病理意义。方法 采用免疫组化SP法检测100例ESCC组织及80例配对癌旁组织芯片中RNF113A的表达。结果 与癌旁正常组织相比，ESCC组织中RNF113A的表达上调，差异有统计学意义(P<0.05)。RNF113A表达与ESCC临床分期(P<0.009)、T分期(P=0.015)相关。Kaplan-Meier生存曲线提示，RNF113A表达与ESCC预后无关(P>0.05)。单因素分析结果显示，患者性别、临床分期、T分期、淋巴结转移及组织学类型影响ESCC患者的总生存期。多因素分析结果显示，肿瘤临床分期、淋巴结转移及组织学类型是ESCC预后的独立危险因素。结论 RNF113A在ESCC组织中高表达，且RNF113A表达程度越高，临床分期及T分期越晚；在RNF113A阳性ESCC中，男性、临床分期及T分期越晚、淋巴结转移阳性的患者术后生存率低，预后差。     

SLP-2在胃癌组织中的表达及其预后意义

 目的：探讨红细胞膜整合蛋白SLP-2（stomatin-like protein 2）在胃癌中的表达及其与临床病理学指标及预后的关系。方法：选取中山大学肿瘤防治中心病理科有完整临床资料的胃癌手术标本190例,应用免疫组织化学方法检测胃癌中SLP-2蛋白的表达,并分析其与临床病理特征及预后的关系。结果：（1）胃癌组织中SLP-2蛋白表达的阳性率为63.2%（120/190）。SLP-2表达与胃癌浸润深度、TNM分期及淋巴结转移有关（P<0.05）,而与患者性别、年龄、肿瘤分化程度、肿瘤直径和远处转移均无关（P>0.05）;（2）Kaplan-Meier 生存曲线分析结果显示：SLP-2阳性表达患者的累积生存率明显低于阴性表达患者（P<0.01）;（3）单因素分析结果显示：SLP-2 的表达、淋巴结转移、肿瘤分化程度、肿瘤直径、TNM分期、浸润深度及远处转移均影响胃癌预后;多因素分析表明,只有肿瘤直径和TNM分期是独立的预后指标。结论：（1）SLP-2在胃腺癌组织中高表达,可能参与胃腺癌的发生发展和转移;（2）SLP-2在一定程度上影响胃癌的预后,其过度表达提示胃癌预后差。     

胃癌中骨桥蛋白与OCT2的表达及意义

目的探讨骨桥蛋白（osteopontin,OPN）及转录因子OCT2在胃癌中的表达及其与临床病理参数及预后的关系。方法应用组织微阵列技术和免疫组化SP法检测99例胃癌组织中OPN蛋白与OCT2蛋白的表达情况。结果99例胃癌中OPN蛋白及OCT2蛋白的阳性表达率分别为60．61％、54．55％;OPN蛋白表达与肿瘤大小、浸润深度、脉管侵犯、淋巴结转移及远处转移呈正相关;OCT2蛋白表达也与肿瘤大小、浸润深度、脉管侵犯、淋巴结转移及远处转移呈正相关;OPN蛋白表达与OCT2蛋白表达呈正相关;OPN及OCT2蛋白阳性表达病例的平均生存时间和5年生存率均明显低于阴性表达的病例。结论OPN及OCT2蛋白表达可预测胃癌浸润和转移,是指导临床治疗及评估预后的有价指标。     

胃癌患者预后及病理因素与Bmi-1表达的相关性研究

目的： 探讨胃癌组织中Bmi-1蛋白的表达与胃癌患者病理因素及预后的相关性。方法： 收集我院2002-2004年146例有3年以上完整随访资料的胃癌术后患者，采用免疫组织化学法对手术标本石蜡切片进行染色，检测Bmi-1蛋白的表达情况，并分析该蛋白表达对胃癌患者临床病理因素及预后的影响。结果： Bmi-1蛋白在本组胃癌中阳性表达率为67.8%（99/146）。Bmi-1的表达与胃癌大小、临床分期、淋巴结转移和侵润深度密切相关（P<0.05），而与患者的性别、年龄、肿瘤分化程度等无关（P>0.05）。Bmi-1阳性表达者生存率明显低于阴性者（P<0.01）。多因素分析显示，Bmi-1表达、癌侵润深度、淋巴结转移、远处转移、肿瘤大小、术后化疗均为具有显著统计学意义的影响预后的因素。结论： Bmi-1在胃癌组织表达状态与胃癌的生长和侵润转移关系密切，可以作为反映胃癌生物学行为和判断预后的有效指标     

胃癌组织中CapG蛋白的表达及其与临床病理特征及预后的关系

目的检测巨噬细胞加帽蛋白(gelsolin-like actin-capping protein,CapG)在胃癌及癌旁组织(距离癌组织边缘5 cm)中的表达,探讨CapG蛋白表达与胃癌临床病理参数及预后的关系。方法收集125例胃癌石蜡包埋组织样本及癌旁组织30例。患者均为未行放、化疗的初诊患者。每例组织样本均行CapG免疫组化染色,并设置对照组。通过病理医师评分来确定CapG蛋白的表达量,探讨CapG蛋白表达与胃癌临床病理参数及预后的关系。结果 CapG蛋白在细胞质和细胞核中均表达,呈棕黄色颗粒状。癌旁组织中基本无表达,胃癌组织中的表达显著高于癌旁组织;胃癌组织中CapG蛋白表达与患者性别、年龄、肿瘤大小、肿瘤位置无显著相关(P均0.05),与浸润深度(P=0.044)、淋巴结转移(P=0.026)、远处转移(P=0.001)及AJCC分期(P=0.012)显著相关。Kaplan-Meier生存曲线显示,CapG蛋白高表达组患者的总体预后较低表达组差,且差异具有显著性(P0.001)。Cox回归分析显示,肿瘤位置、淋巴结转移、远处转移、AJCC分期、CapG蛋白表达情况是胃癌患者预后的独立危险因素。结论 CapG蛋白在胃癌组织中高表达,可能与胃癌的发生、发展有关,可作为胃癌预后判断的指标之一,有望成为胃癌治疗的潜在新靶点。     

肿瘤干细胞表面标记物CD44在胃癌浸润和淋巴结转移中的作用

背景：肿瘤干细胞不仅能启动肿瘤发生,还参与肿瘤细胞的侵袭和转移。对肿瘤干细胞来说,识别其特异性细胞表面标志物已成为研究热点。 目的：探讨肿瘤干细胞表面标记物CD44在胃癌浸润和淋巴结转移中的临床意义。 方法：采用免疫组化 SABC法检测胃癌组织标本CD44蛋白表达,应用Pearsonχ2检验和Cox回归多因素分析,确定CD44表达与胃癌生物学特性及其预后的相关性。 结果与结论：100例胃癌标本中,59例(59.0%)标本CD44蛋白呈阳性表达。CD44蛋白在距胃癌原发灶边缘5 cm以上的正常胃黏膜组织中呈阴性表达。胃癌组织中CD44蛋白广泛表达,主要表达于细胞膜,少量表达于细胞浆。胃癌组织中 CD44蛋白的表达和患者性别、年龄无关(P > 0.05),但与肿瘤分期和淋巴管浸润、组织学分级、肿瘤大小等有关(P < 0.05),其中,肿瘤浸润越深、组织学分级越高、肿瘤直径越大、有淋巴结转移,则CD44蛋白表达阳性率越高,CD44阳性表达是影响患者术后生存的独立预后因素(P < 0.05)。以上结果表明肿瘤干细胞表面标记物CD44在胃癌组织中的表达与胃癌的浸润和淋巴结转移密切相关,表达越高患者预后越差。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

胃癌组织中CKS2蛋白表达与患者预后的相关性

目的探讨胃癌组织中CKS2蛋白表达与临床病理特征及患者预后的相关性。方法应用qRT-PCR和免疫组化法检测CKS2基因及蛋白在胃癌及癌旁组织中的表达水平,并探讨其与胃癌患者预后的相关性。结果胃癌组织中CKS2基因的表达水平(0.97±0.16)高于癌旁组织(0.38±0.11,P0.05);胃癌组织中CKS2蛋白的表达水平(21/203,59.60%)与Lauren分型、肿瘤浸润深度、淋巴结转移以及TNM分期密切相关(P0.05)。胃癌患者预后及生物信息学分析结果进一步证实,CKS2蛋白表达水平与胃癌患者不良预后相关(P0.05)。结论 CKS2蛋白在胃癌组织中的高表达水平与胃癌发生、发展密切相关,可作为评估胃癌患者预后的独立因素之一。     

FOXM1和E-cadherin在胃癌组织中的表达

目的探讨FOXM1和E-cadherin蛋白在胃癌组织中的表达及与临床病理特征、预后的关系。方法应用免疫组化法检测胃癌组织芯片中FOXM1、E-cadherin蛋白的表达,分析其与胃癌临床病理特征与其预后的关系。结果FOXM1蛋白在胃癌组织中高表达并与肿瘤临床分期、淋巴结转移、患者年龄、肿瘤大小、分化程度及脉管浸润密切相关(P 0. 05); FOXM1阳性者生存期明显低于阴性者;而Ecadherin表达与之相反,FOXM1表达与E-cadherin的表达呈负相关(rs=-0. 198,P=0. 019)。结论 FOXM1高表达和E-cadherin低表达在胃癌的浸润、转移及生存中可能起到潜在的关键作用。     

CEACAM1和CD34蛋白表达与胃癌侵袭转移的关系

目的探讨癌胚抗原相关黏附分子1(CEACAM1)和CD34蛋白表达与胃癌侵袭转移的关系。方法免疫组化SP法检测90例胃癌组织和30名正常胃黏膜组织中CEACAM1及CD34的表达情况,分析CEACAM1和CD34标记的微血管密度(MVD)与胃癌患者临床病理特征的关系。结果 CEACAM1和CD34蛋白在胃癌中的阳性表达明显高于正常胃黏膜组织(P0.05)。CEACAM1蛋白的表达程度与肿瘤分化、侵袭深度、是否淋巴结转移及病理分期相关(P0.05),胃癌组织中MVD与肿瘤大小、分化、侵袭深度、是否淋巴结转移及病理分期相关(P0.05)。CEACAM1表达程度及CD34标记的MVD在胃癌中的表达呈正相关关系(P0.05)。结论 CEACAM1与CD34参与了胃癌的侵袭和转移,有望成为胃癌发生、发展和预后的预测指标。     

胃癌组织中PD-L1蛋白表达和基因扩增的相关性北大核心CSCD

目的探讨胃癌中程序性死亡分子配体1（PD-L1）蛋白表达和基因扩增的相关性及与临床病理特征的相关关系。方法选取山西省肿瘤医院2011年有完整随访资料和临床病理资料的胃癌患者247例,应用免疫组织化学（IHC）标记及荧光原位杂交（FISH）技术检测胃癌组织中PD-L1蛋白表达和基因扩增情况。结果（1）PD-L1蛋白表达与胃癌临床病理特征的关系：在胃癌组织,肿瘤细胞中PD-L1蛋白表达阳性率为25.9%（64/247）,肿瘤浸润免疫细胞（IC）中PD-L1蛋白表达阳性率为26.7%（66/247）,两者表达具有相关性（P〈0.01）,肿瘤细胞中PD-L1表达与分化程度和肿瘤直径有相关性（P〈0.05）,免疫细胞中PD-L1表达与有无脉管癌栓有相关性（P〈0.05）。（2）PD-L1基因扩增与胃癌临床病理特征的关系：FISH检测PD-L1基因扩增率为19.0%（47/247）。PD-L1基因扩增与年龄、胃大/小弯、肿瘤部位、肿瘤直径及淋巴结转移有相关性（P〈0.05）。（3）IHC检测的肿瘤细胞中PD-L1蛋白表达与FISH检测的PD-L1基因扩增,两种检测方法阳性符合率为25.0%（16/64）,阴性符合率为83.0%（152/183）,总符合率为68.0%（168/247）,IHC和FISH检测结果一致性较差（P＝0.157）。（4）单因素生存分析：肿瘤细胞中PD-L1蛋白表达与预后呈负相关关系,免疫细胞中PD-L1蛋白表达和PD-L1基因扩增与预后均没有明显相关性。脉管癌栓、肿瘤直径、浸润深度和淋巴结转移均是胃癌的不良预后因素（P〈0.05）。（5）多因素Cox回归分析：肿瘤细胞中PD-L1蛋白表达、浸润深度和淋巴结转移均为影响胃癌预后的独立危险因素（P〈0.05）。结论胃癌中PD-L1蛋白表达与基因扩增一致性较差;PD-L1蛋白表达提示预后较差;PD-L1基因扩增与预后无明显相关性。     

Clinicopathologic Characteristics and Prognosis of Advanced Gastric Cancer Simulating Early Gastric Cancer

Background

Although the clinicopathologic features and prognosis of Borrmann type advanced gastric cancer has been well characterized, those of advanced gastric cancer simulating early gastric cancer (AGC simulating EGC) still remains unclear.

Methods

We reviewed 1985 gastric cancer patients who had undergone gastrectomy at our hospital to determine the clinicopathologic characteristics, susceptible sites for lymph node metastasis, and prognosis of AGC simulating EGC in comparison with Borrmann type advanced gastric cancer.

Results

Among 102 patients with AGC simulating EGC, 100 patients (98%) had tumors with depressed type appearance. The frequencies of serosal invasion, lymph node metastasis, lymphatic vessel invasion, blood vessel invasion, and liver metastasis were significantly lower in AGC simulating EGC than in Borrmann type tumors. The prognosis of AGC simulating EGC was significantly better than that of the Borrmann type tumors. Multivariate analysis indicated that the gross appearance was an independent prognostic factor. In patients with AGC simulating EGC which invaded to the the muscularis propria (MP), most lymph node metastasis was restricted with the perigastric lymph nodes (1st-titer lymph nodes) and lymph node metastasis to 2nd-titer lymph nodes was only observed at station 8a.

Conclusion

AGC simulating EGC is less advanced in comparison with Borrmann type advanced gastric cancer. Based on the results of susceptible sites for lymph node metastasis in the current study, limited lymph node dissection could be indicated for AGC simulating EGC whose depth of invasion is MP.     

Heparanase expression correlates with invasion and poor prognosis in gastric cancers

Degradation of basement membrane and extracellular matrix structures are important features of the metastatic process of malignant tumors. Human heparanase degrades heparan sulfate proteoglycans, which represent the main components of basement membranes and the extracellular matrix. Because of the role of heparanase in tumor invasion and metastasis, we examined heparanase expression in primary gastric cancers and in cell lines derived from gastric cancers by immunohistochemistry and RT-PCR, respectively. Four of seven gastric cancer cell lines showed heparanase mRNA expression by RT-PCR. Heparanase protein was detected in both the cytoplasm and the nucleus of heparanase mRNA-positive cells by immunohistochemical staining. Heparanase expression was confirmed in 35 (79.5%) of 44 gastric tumor samples by immunohistochemical staining. However, no or weak heparanase expression was detected in normal gastric mucosa. In situ hybridization showed that the mRNA expression pattern of heparanase was similar to that of the protein, suggesting that increased expression of the heparanase protein at the invasive front was caused by an increase of heparanase mRNA in tumor cells. Analysis of the clinicopathologic features showed stronger heparanase expression in cases of huge growing tumors, extensive invasion to lymph vessels, and regional lymph node metastasis. In gastric cancer, patients with heparanase expression showed significantly poorer prognosis than those without such expression (p = 0.006). In conclusion, our findings suggest that high expression of heparanase in gastric cancer is a strong predictor of poor survival.     

Histopathological predictor for regional lymph node metastasis in gastric cancer

Regional lymph node metastasis in gastric cancer is a definitive indicator of the patient’s prognosis. The goal of this study was to identify the predictors for lymph node metastasis among all the possible histopathological parameters, especially by conducting an objective discrimination of the lymphatic and blood vessels. A total of 210 resected primary gastric cancers with or without lymph node metastasis were evaluated based on the conventional histopathological parameters together with immunohistochemistry using antisera-recognizing lymphatic endothelial hyaluronan receptor-1 (LYVE-1), von Willebrand factor, and lymphangiogenesis promoter vascular endothelial growth factor-C (VEGF-C) antibodies. A multivariate regression analyses of the results indicated that only lymphatic invasion was a significant independent predictor of lymph node metastasis at any stage of cancer invasion. VEGF-C expression was partially related to lymph node metastasis in early gastric cancer. The identification of lymphatic invasion by LYVE-1 antibody is therefore useful to predict regional lymph node metastasis in gastric cancer.     

Tissue microarray analysis reveals strong clinical evidence for a close association between loss of annexin A1 expression and nodal metastasis in gastric cancer

Aims Annexin A1 (ANXA1) is a calcium- and phospholipid-binding protein that has been implicated in the regulation of inflammation, cell proliferation, and apoptosis. Its role in tumor development and progression is controversial, whereas its role in gastric cancer is unknown. We investigated ANXA1 expression and determined its clinical significance in gastric cancer. Methods and results Tissue microarray blocks containing primary gastric cancer, lymph node metastasis, and adjacent normal mucosa specimens obtained from 1,072 Chinese patients were constructed. Expression of ANXA1 in these specimens was analyzed using immunohistochemistry. Complete loss of ANXA1 expression was observed in 691 (64%) of the 1,072 primary tumors and 146 (86%) of 169 nodal metastases. Loss of ANXA1 expression was significantly associated with advanced T stage, lymph node metastasis, advanced disease stage, and poor histological differentiation. Loss of ANXA1 expression correlated significantly with poor survival rates in both univariate and multivariate analyses. Conclusions ANXA1 expression decreased significantly as gastric cancer progressed and metastasized, suggesting the importance of ANXA1 as a negative biomarker for gastric cancer development and progression.     

肿瘤干细胞表面标记物CD44在胃癌组织中的表达及意义

BACKGROUND:Studies have shown that CD44 expression is closely associated with malignant transformation of gastric cancer. OBJECTIVE:To study the expression of CD44 in gastric cancer tissues and its clinical significance. METHODS:Gastric cancer specimens from 94 cases of gastric cancer after surgery and normal gastric tissue specimens from 30 cases undergoing gastroscope examination were collected and detected using S-P method. The positive expression rate of CD44 protein in these two groups was compared, and the relationship between CD44 and prognosis was analyzed. RESULTS AND CONCLUSION:The positive expression rate of CD44 protein in the gastric cancer group (73%) was significantly higher than that in the normal group (3%) (P < 0.05). The positive expression rate of CD44 protein in gastric cancer patients was remarkably associated with TNM stage, differentiation degree, invasion depth and lymph node metastasis (P < 0.05). The 3-year survival rate of gastric cancer patients positive for CD44 protein was significantly lower than that of negative patients (P < 0.05). The higher TNM staging indicated the lower differentiation degree, and lymph node metastasis and CD44 positive expression were independent risk factors (P < 0.05). To conclude, the expression of CD44 protein is related to the clinical pathological features and prognosis of gastric cancer patients to some extents.     

胃癌浸润转移的螺旋CT征象与PTEN表达的相关性

目的:探讨胃癌螺旋CT(SCT)征象与磷酸酶基因(PTEN)表达之间的潜在联系,以及与临床病理的相关性.方法:选择进展期胃癌患者60例,术前一周进行SCT三期增强扫描,术后标本分别进行HE染色读片及免疫组化染色SP法检测PTEN表达.结果:SCT示浆膜侵犯判断的准确性为91.66%(55/60),淋巴结转移判断准确性为...     

胃癌组织中PD-L1的表达及其与预后的关系

为探讨共刺激分子PD-L1在胃癌组织中的表达及其临床意义。用免疫组织化学方法检测102例胃癌和10例胃腺瘤PD-L1的表达,并对其表达与患者年龄、性别、胃癌部位、肿瘤大小、组织类型、肿瘤浸润深度、分化程度、淋巴结转移等进行相关分析。结果:胃腺瘤组织和正常胃组织不表达PD-L1分子,胃癌组织中PD-L1呈阳性表达,表达阳性率为42.2%;PD-L1分子在胃癌组织中的表达与胃癌患者年龄、性别、肿瘤部位、组织学类型无关(P>0.05),与肿瘤大小、肿瘤的浸润深度、淋巴结转移及预后有关。当肿瘤大于5cm(P<0.05)、肿瘤浸润达深肌层、淋巴结转移阳性、生存期<2年时,PD-L1表达阳性率明显升高(P<0.01)。多变量分析还显示,PD-L1分子可作为评估胃癌预后的独立因素。胃癌组织PD-L1分子的检测有助于胃癌预后的判断和作为个体化治疗选择的生物学指标。