乳腺癌组织中癌基因STAT3的表达及临床意义

目的 检测乳腺癌组织及癌旁组织中信号转导子与转录活化子3（STAT3）的表达，探讨其表达与乳腺癌各临床病理因素之间的关系：方法 利用SABC免疫组织化学技术检测66例乳腺痛组织及其癌旁组织中STAT3蛋白的表达。结果 乳腺癌组织中STAT3蛋白明显高于癌旁组织，低分化乳腺癌组织中STAT3表达水平明显高于高分化乳腺癌，有淋巴结转移的乳腺癌中STA33表达明显高于无淋巴结转移的乳腺癌。结论 STAT3表达与乳腺癌的组织分化程度及淋巴结转移有关，STAT3过度表达可能在乳腺癌的发生、发展过程中起重要作用。     

C-Jun蛋白在食管鳞癌组织中的表达及临床意义

目的:探讨C-Jun蛋白在食管鳞癌(esophageal squamous cell carcinoma,ESCC)患者组织中的表达及其与临床生物行为之间的关系.方法:运用免疫组织化学及RT-PCR方法检测96例ESCC患者癌组织及相应癌旁织中C-Jun蛋白的表达情况,分析C-Jun蛋白表达于ESCC临床生物学行为的关系.结果:C-Jun在ESCC患者癌组织中的表达(0.7703±0.3330)高于癌旁组织(0.2546±0.1328),差异有统计学意义(t=-11.23,P<0.05),并且C-Jun蛋白在ESCC组织中的表达与肿瘤淋巴转移及TNM分期相关(P<0.05).结论:C-Jun蛋白在ESCC组织中高表达,与肿瘤淋巴转移及TNM分期相关,可能与ESCC的发生发展相关.     

STAT3蛋白在肝癌组织中的表达及临床意义

目的探讨STAT3和p-STAT3蛋白在肝癌组织中的表达及其临床意义。方法采用免疫组织化学的方法检测了90例肝癌组织及其相应的癌旁组织中STAT3和p-STAT3蛋白的表达,分析STAT3和p-STAT3蛋白表达与临床病理特征及患者预后的关系。特征参数之间用χ2检验;采用Kaplan-Meier法进行生存分析,用Log-rank检验进行曲线间比较;运用Cox回归进行单因素及多因素生存分析。结果肝癌组织中STAT3主要在细胞质中表达,而p-STAT3主要表达在细胞核内;STAT3和p-STAT3在肝癌组织中阳性表达率明显高于癌旁组织;STAT3和p-STAT3蛋白的表达与卫星灶（P=0.033,P〈0.01）、血管浸润（P=0.046,P〈0.01）及AJCC分期（P〈0.01,P〈0.01）有关,与患者的性别（P=0.280,P=0.403）、年龄（P=0.432,P=0.844）、肿瘤大小（P=0.762,P=0.161）、肿瘤数量（P=0.301,P=0.326）、肿瘤的分化程度（P=0.753,P=0.910）及甲胎蛋白（P=0.441,P=0.080）比较差异无统计学意义;肝癌组织中STAT3和p-STAT3蛋白高表达的患者5年生存率明显低于低表达患者。结论 STAT3和p-STAT3蛋白可能参与了肝癌的浸润转移,有望成为一种新的肝癌预后参考指标。     

食管鳞癌组织中HIWI的表达变化及意义

目的观察食管鳞状细胞癌组织中干细胞标记物HIWI蛋白表达变化,并探讨其临床意义。方法采用免疫组织化学SP法检测133例手术切除的食管鳞癌组织及15例正常食管上皮组织中的HIWI蛋白,分析其表达与患者临床病理参数的关系。结果食管癌组织和正常食管上皮组织中HIWI的阳性表达率分别为52.8%和6.7%,两组相比P<0.05。食管癌组织中HIWI表达与食管癌分化程度、临床分期有关(P<0.05)。结论食管癌组织中HIWI表达上调。HIWI参与了食管癌的发生发展过程。     

食管鳞癌组织中PTEN、Livin蛋白的表达变化及意义

目的观察食管鳞癌组织中PTEN、Livin蛋白表达的变化,并探讨其意义。方法采用免疫组化SP法检测60例食管鳞癌组织及20例癌旁正常食管组织中的Livin、PTEN蛋白。结果食管鳞癌组织中Livin、PTEN蛋白阳性率分别为70.0%、36.7%,癌旁正常食管组织为45.0%、90.0%,两者比较,P均〈0.05;食管鳞癌组织中Livin、PTEN蛋白表达均与癌组织分化程度及有无淋巴结转移有关（P均〈0.05）,且二者的表达呈负相关（r=-0.330,P〈0.05）。结论PTEN蛋白低表达及Livin蛋白高表达在食管鳞癌的发生发展中起重要作用。     

食管鳞癌组织中B7-H4、CD3表达变化及意义

目的探讨B7-H4、CD3在食管鳞癌发生、发展中的作用。方法采用免疫组化SP法检测30例食管鳞癌组织（食管癌组）和20例癌旁正常食管黏膜组织（对照组）中B7-H4、CD3蛋白表达,采用等级相关方法分析B7-H4和CD3表达的相关性。结果食管癌组B7-H4阳性表达率高于对照组,CD3阳性表达率低于对照组（P均〈0.05）。不同临床分期及淋巴结转移情况者食管癌组织中B7-H4表达差异有统计学意义（P均〈0.05）。食管癌组织中B7-H4与CD3蛋白的表达呈负相关关系（r=-0.467,P〈0.05）。结论食管鳞癌组织中B7-H4呈高表达,CD3呈低表达,二者与食管鳞癌的发生发展及侵袭转移有关。     

食管鳞癌组织中p34^cdc2的表达变化及意义

目的观察人食管鳞癌组织中细胞分裂周期蛋白p34^cdc2的表达,并探讨其临床意义。方法利用组织芯片技术结合免疫组化及蛋白免疫印迹法检测138例食管癌患者肿瘤组织和配对正常食管黏膜组织中的p34^cdc2蛋白。结果p34^cdc2在食管鳞癌组织的表达明显高于配对正常黏膜组织,P〈0.01。p34^cdc2表达与食管鳞癌临床分期、淋巴结转移有关（P均〈0.05）,与分化程度和肿瘤浸润深度等无关（P均〉0.05）。结论食管癌组织中p34^cdc2表达升高。p34^cdc2可促进食管癌的发生与发展。     

食管鳞癌组织中MICA基因mRNA、蛋白表达及意义

目的探讨MHCⅠ类链相关蛋白A（MICA）与食管鳞癌分化程度及淋巴结转移的相关性。方法采用RT-PCR法检测43例食管鳞癌组织（鳞癌组）和相应癌旁正常组织（癌旁组）中MICA mRNA表达,免疫组化SP法检测两组MICA蛋白表达,Spearman相关关系检验分析其相关性：结果鳞癌组MICA mRNA的表达水平显著高于癌旁组（t=8．35,P〈0．05）。鳞癌组MICA蛋白表达与癌组织分化程度及淋巴结转移有相关性,与肿瘤大小、性别、年龄无相关性（P〉0．05）;MICA蛋白表达水平与MICA mRNA表达水平呈显著正相关（rs=0．905,P〈0．01）。结论MICA高表达与食管鳞癌组织分化程度密切相关,可能在食管鳞癌的发生发展、浸润转移过程中起重要作用。     

Notch-1和TMEM16A在食管鳞癌组织中表达及临床意义

目的探讨Notch-1和TMEM16A在食管鳞癌组织中表达及临床意义。方法采用免疫组化S-P法检测55例食管鳞癌组织中Notch-1和TMEM16A蛋白表达,并分析二者与食管鳞癌患者临床病理特征之间关系。结果食管鳞癌组织中Notch-1表达显著低于正常食管组织(P<0.05),而TMEM16A表达显著高于正常食管组织(P<0.05),二者表达呈负相关(r=-0.497,P=0.001)。二者表达均与食管鳞癌分化程度和淋巴结转移有关。Notch-1蛋白表达还与TNM分期、肿瘤浸润深度有关(P<0.05),结论食管鳞癌组织中Notch-1和TMEM16A蛋白表达呈负相关,二者在食管鳞癌发生、发展及生物学行为过程中可能起重要作用。     

食管鳞癌组织CD44V6蛋白的表达及意义

CD44 V6 基因蛋白的特异性表达与恶性肿瘤的发生发展、侵袭转移和预后密切相关。我们用流式细胞仪检测了食管鳞癌组织中 CD44 V6 蛋白的表达 ,分析其与食管鳞癌各种临床病理指标的关系 ,探讨 CD44 V6 蛋白检测在食管鳞癌患者预后判断中的价值。临床资料 :食管癌组织取自 5 2例患者 ,男 3 6例 ,女 16例 ;年龄 3 7～ 68岁 ,中位年龄 5 2岁。术前未接受放疗和化疗。术后病理检查确诊均为鳞癌。癌肿位于食管上段 5例 ,中段 3 3例 ,下段 14例 ;大体病理分型为溃疡型 3 5例 ,髓质型 9例 ,蕈伞型 8例 ;病理分级 级 18例 , 级 2 4例 , 级 10例 …     

Expression of FOXP3 in esophageal squamous cell carcinoma relating to the clinical data

Forkhead box protein 3 (FOXP3) has been studyed as a biomarker in many human malignancies recently. But in esophageal squamous cell carcinoma (ESCC) the studies are limited. In this study, expression of FOXP3 in ESCC tissue was evaluated in relation to the clinical data. Detection of FOXP3 mRNA was made by using quantitative real‐time PCR while protein expression was assessed by immunocytochemistry (n = 112). The results were correlated to the clinical data including age, gender, carcinoma size, carcinoma differentiation, lymphatic invasion and pathological stage. A significantly higher FOXP3 expression in tumors was confirmed than in normal‐appearing mucosa. The FOXP3 mRNA and protein expressions were higher in advanced stages (stage II B and III) than in early stages (stage I and stage II A). A significantly higher FOXP3 expression in tumors with lymph node metastasis was also confirmed than in those without lymph node metastasis. No significant correlation was found in age, gender, carcinoma size, or carcinoma differentiation. These results suggest that expression of FOXP3 was higher in ESCC tissue and was closely correlated to lymphatic invasion and pathological stage. It may imply that FOXP3 might play an important role in esophageal carcinoma progression.     

食管鳞癌组织中MMP-2和E-cadherin的表达及其意义

目的探讨食管鳞癌组织和食管鳞癌细胞系Eca109、EC9706中MMP-2和E—cadherin的表达及其与食管鳞癌临床病理特征的关系。方法应用免疫组化S-P法检测100例食管鳞癌组织及食管鳞癌细胞系Eca109、EC9706中MMP-2和E—cadherin蛋白的表达,应用RT—PCR技术检测两株细胞系中MMP-2mRNA和E—cadherinmR—NA的表达。结果食管鳞癌组织中MMP-2蛋白阳性率明显高于正常黏膜组织（P〈0．01）,且与癌组织的分化程度、浸润深度、淋巴结转移密切相关（P〈0．05）;E—cadhefin蛋白在食管鳞癌组织中阳性率明显低于正常黏膜组织（P〈0．01）,与癌组织分化程度、有无淋巴结转移呈负相关（P〈0．05）,与浸润深度无明显相关性（P〉0．05）;MMP-2和E—cadherin在食管鳞癌中的表达呈负相关（P〈0．01）;细胞系中MMP-2mRNA和E—cadherinmRNA的表达有显著性差异（P〈0．01）。结论食管鳞癌组织中MMP-2呈高表达;E—cadherin呈低表达,二者对食管癌的发生、浸润转移具有相反的调节作用;联合检测其变化可更准确预测食管癌的恶性生物学行为。     

Risk factors of lymph node metastasis in T1 esophageal squamous cell carcinoma

Background and Aim: To perform endoscopic mucosal resection (EMR) for T1 esophageal cancer, it is essential to estimate the lymph node status exactly. In order to evaluate the feasibility of EMR for esophageal cancers, we evaluated the clinicopathological features of T1 esophageal squamous carcinomas with an emphasis on the risk factors and distribution patterns of lymph node metastasis. Methods: From 1994 to 2006, a total of 200 patients with T1 esophageal carcinoma were treated surgically in our institution. Among them, clinicopathological features were evaluated for 197 consecutive patients with T1 squamous cell carcinoma. Results: The frequency of lymph node involvement was 6.25% (4/64) in mucosal cancers and 29.3% (39/133) in submucosal cancers (P < 0.001). In patients with M1 (n = 32) and M2 (n = 14) cancers, no lymph node metastasis was found. In multivariate analysis, size larger than 20 mm, endoscopically non‐flat type, and endo‐lymphatic invasion were significant independent risk factors for lymph node metastasis. The differentiation of tumor cell was not a risk factor for lymph node metastasis. Conclusions: We suggest that EMR may be attempted for flat superficial squamous esophageal cancers smaller than 20 mm. After EMR, careful histological examination is mandatory.     

Survivin和Ki67在食管鳞癌组织中的表达及意义

目的探讨Survivin和Ki67蛋白表达在食管鳞癌发生、发展中的作用。方法应用免疫组化SP法检测40例食管鳞癌患者癌组织中Survivin和Ki67蛋白表达情况,并分析其与临床特征的关系以及二者的相关性。结果食管鳞癌患者癌组织中Survivin和Ki67蛋白的阳性表达率分别为72．5％和75．0％。两种蛋白表达与肿瘤组织分化程度、浸润程度相关,而与性别、年龄、淋巴结转移情况无关。二者表达呈显著正相关（r=0．420,P〈0．05）。结论Survivin和Ki67蛋白与食管鳞癌组织的分化和恶性进展有关,Survivin在抑制细胞凋亡的同时可能促进了细胞增殖。     

Expression of klotho and β‐catenin in esophageal squamous cell carcinoma,and their clinicopathological and prognostic significance

Esophageal carcinoma is one of the most common types of cancers in the world; the molecular mechanism underlying its tumorigenesis is still not well understood. This study was aimed at investigating the expression of klotho and β‐catenin in patients with esophageal squamous cell carcinoma (ESCC) and analyzing their association with clinicopathological variables and their effects on prognosis. The expression patterns of klotho and β‐catenin were determined by tissue microarray and immunohistochemical technique in ESCC and normal tissues, and their correlations with clinicopathological characteristics were investigated using univariate and multivariate analysis. The serum klotho levels in 40 ESCC patients and controls were measured by sandwich enzyme‐linked immunosorbent assay system (ELISA). The expression level of klotho was significantly lower in ESCC than in the adjacent noncancerous tissues (30 vs. 50%, P < 0.000), and the protein level was negative correlated with clinical staging, histological grade, lymph node metastasis, and invasion depth (P < 0.05). Whereas, the expression of β‐catenin was much higher in ESCC than their corresponding normal mucosa tissues (78.3 vs. 11.5%, P < 0.000), and the level of protein correlated only with histological grade and invasion depth (P < 0.05). Correlation analysis showed the expression level of klotho inversely correlated with that of β‐catenin (r = ?0.214, P < 0.01). Patients with klotho‐positive tumors had longer survival than those with klotho‐negative tumors (P < 0.01). Cox proportional hazards model analysis demonstrated that positive expression of klotho was an important factor indicating good prognosis (hazard ratio, 0.371; 95% confidence interval, 0.201–0.685; P < 0.01). ELISA showed that the level of serum klotho was markedly higher (461.50 ± 43.30 pg/mL) than control group (239.37 ± 20.65 pg/mL) (P < 0.001). Receiver operating characteristic analysis gave a cut‐off value of 327.031 of serum klotho with a sensitivity of 81.3% and specificity of 81.2% (P < 0.000). Our present study demonstrated for the first time that klotho might be a novel biomarker candidate for predicting progression and prognosis in patients with ESCC.     

食管鳞癌组织中JWA、FAK表达变化及其与淋巴结转移的关系

目的观察食管鳞癌组织中JWA蛋白和黏着斑激酶（FAK）的表达变化,并探讨其与食管鳞癌淋巴结转移的关系。方法采用蛋白免疫印迹法检测37例食管鳞癌患者肿瘤组织及其癌旁组织中的JWA、FAK蛋白。结果食管鳞癌组织与癌旁组织中JWA蛋白的相对表达量分别为0.302±0.119、0.638±0.128,FAK分别为0.717±0.153、0.432±0.097,二者JWA、FAK蛋白表达量相比,P均〈0.05。有、无淋巴结转移者JWA蛋白相对表达量分别为0.163±0.37、0.383±0.06,FAK蛋白分别为0.832±0.134、0.658±0.109,P均〈0.05。JWA、FAK蛋白在食管鳞癌组织中的表达呈负相关（r=-0.736,P〈0.01）。结论食管鳞癌组织中JWA蛋白表达下调,FAK蛋白表达上调,且其表达变化与食管鳞癌淋巴结转移有关。JWA可能通过抑制FAK的表达,发挥抑制食管鳞癌淋巴结转移的作用。     

Immunohistochemical analysis of nuclear survivin expression in esophageal squamous cell carcinoma

Despite advances in the treatment of esophageal carcinoma, the prognosis for this disease remains poor. Therefore, it is important to obtain a better understanding of the molecular basis of esophageal carcinogenesis. The purpose of this study was to clarify the roles of survivin in esophageal squamous cell carcinoma (ESCC). One hundred 22 ESCC surgical specimens resected from 1989 to 1999 were examined. Survivin expression was assessed by immunohistochemistry. Tumor cells were considered survivin-positive if the immunoreactivity was confined to the nucleus, and a scoring method was applied. Survivin-positive immunostaining was detected in 68 patients (56%). There was a significant association between survivin expression and pN (P = 0.0472). Moreover, the overall survival rate was worse in patients with survivin-positive tumors than in patients with survivin-negative tumors (P = 0.0189). The overexpression of survivin was associated with the overall survival rate and poor prognosis in patients with ESCC. Survivin may be targeted during cancer therapy because of its selective expression in malignant tissue.     

Expression of midkine and its clinical significance in esophageal squamous cell carcinoma

AIM: TO investigate the expression of midkine in esophageal squamous cell carcinoma (ESCC) and analyze its relationship with clinicopathological features. METHODS: RT-PCR and immunocytochemical staining were used to detect the expression of midkine mRNA and protein in EC109 cells, respectively. Then the expression of midkine in 66 cases of ESCC samples were detected by immunohistochemistry using monoclonal antibodies against human midkine. RESULTS: Midkine was expressed in EC109 cell by RT-PCR and immunocytochemistry. The immunoreactivity was detected in 56.1% (37/66) of the ESCC samples. The expression of midkine was found in cytoplasm of tumor cells. Notably, the intensity of midkine was stronger at the area abundant in vessels and the invading border of the tumors. Midkine was more intensely expressed in well differentiated tumors (76.9%) than in moderately and poorly differentiated tumors (43.1% and 41.2%, respectively) (P<0.05). There was no statistically significant correlation between midkine expression and gender, age, clinical stage, lymph node metastasis or survival in ESCC. CONCLUSION: Midkine is overexpressed in ESCC. It may play a role in tumor angiogenesis and invasion. The expression of midkine is correlated with tumor cell differentiation in ESCC. The more poorly tumor cells differentiate, the weaker midkine expresses.