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。     

Expression and prognostic relevance of p21WAF1 in stage III esophageal squamous cell carcinoma

The prognostic effect of p21^WAF1 expression on esophageal squamous cell carcinoma patients is controversial. Further clarifying the effect of this protein is beneficial for optimizing the patient outcomes. In the current study, we investigated the expression of p21^WAF1 protein in 189 specimens of stage III ESCC by immunohistochemistry. As shown by the Kaplan–Meier curve, the overall survival rate of the positive‐expression group was significantly higher than that of the negative‐expression group (P < 0.05). No significant correlation was observed between p21^WAF1 expression and clinicopathological parameters in terms of gender, age, tumor location, tumor grade, pathological stage, and number of regional lymph node metastases (P > 0.05). We concluded that p21^WAF1 played an intricate role in the tumorigenesis and development of ESCC. p21^WAF1 could serve as a positive prognostic predictor for stage III ESCC patients.     

食管鳞癌组织中STAT3蛋白的表达及临床意义

目的 探讨食管鳞癌组织和癌旁正常黏膜组织中信号转导子和转录激活子3（STAT3）的表达及与食管鳞癌发生发展的关系.方法 应用免疫组化SP法检测122例食管鳞癌及其癌旁正常黏膜组织中STAT3蛋白的表达.结果 食管鳞癌组织中STAT3蛋白表达阳性率为89.3%,明显高于癌旁正常黏膜组织的77%（P＜0.05）.Ⅰ级、Ⅱ级、Ⅲ级食管鳞癌组织中STAT3蛋白的阳性率分别为73.7%、89.5%和100%,Ⅲ级中STAT3蛋白的阳性率显著高于Ⅰ级（P＜0.05）.浸润至深层（深肌层和外膜）的食管鳞癌组织中STAT3蛋白阳性表达率为92.8%,明显高于浸润至浅层（黏膜和浅肌层）食管鳞癌组织的76%（P＜0.05）.STAT3的表达与淋巴结转移无关（P＞0.05）.结论 STAT3蛋白过度表达与食管鳞癌的发生发展及恶性演进有关,STAT3有望成为评估食管癌预后的一个新标志物.     

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。     

内皮抑素在食管鳞癌中的表达及其意义

目的研究内皮抑素在食管鳞癌中的表达及其意义。方法采用免疫组化SP法检测内皮抑素在62例食管鳞癌中的表达。结果食管鳞癌组织内皮抑素阳性表达率高于切缘组织和食管良性病组织（P〈0．01）,食管鳞癌内皮抑素表达水平与原发肿瘤的浸润深度、远处转移情况、细胞分化程度、临床TNM分期均有密切关系（P均〈0．05）,而与原发肿瘤部位、区域淋巴结转移状况以及食管鳞癌患者的年龄、性别、饮食习惯、家族史等均无明显关系（均P〉0．05）。结论内皮抑素可能在抑制食管鳞癌侵袭和转移过程中发挥重要作用,可以作为判断其预后的指标之一。     

食管鳞癌组织中IGF-1R、VEGF-C的表达变化及意义

目的观察食管鳞癌组织中的胰岛素样生长因子-1R（IGF．1R）、血管内皮生长因子C（VEGF—C）的表达变化,并探讨其意义。方法分别采用免疫组化法、免疫印迹法检测食管鳞癌和癌旁正常食管组织中的IGF-1R、VEGF—C。结果食管鳞癌组织中IGF-1R、VEGF—C阳性率分别为81．05％、67．37％,癌旁组织中分别为20％、5％,P均〈0．01;食管鳞癌组织中IGF—IR、VEGF．C蛋白条带灰度比值分别为0．58土0．03、0．43±0．05,癌旁组织中分别为0．43±0．02、0．31±0．04,P均〈0．05。IGF—IR、VEGF—C表达与食管鳞癌淋巴结转移、浸润深度有关（P均〈0．01）,二者表达呈正相关（r=0．29,P〈0．05）。结论食管鳞癌组织中IGF—IR、VEGF—C高表达,在食管鳞癌的发生发展及转移中有重要作用。     

Programmed death ligand-1 expression and its prognostic role in esophageal squamous cell carcinoma

AIM To investigate the expression and prognostic role of programmed death ligand-1(PD-L1) in locally advanced esophageal squamous cell carcinoma(ESCC).METHODS A total of 200 patients with ESCC who underwent radical esophagectomy with standard lymphadenectomy as the initial definitive treatment in Seoul National University Hospital from December 2000 to April 2013 were eligible for this analysis. Tissue microarrays were constructed by collecting tissue cores from surgical specimens, and immunostained with antibodies directed against PD-L1, p16, and c-Met. Medical records were reviewed retrospectively to assess clinical outcomes. Patients were divided into two groups by PD-L1 status, and significant differences in clinicopathologic characteristics between the two groups were assessed. RESULTS Tumor tissues from 67 ESCC patients(33.5%) were PDL1-positive. Positive p16 expression was observed in 21 specimens(10.5%). The H-score for c-Met expression was ≥ 50 in 42 specimens(21.0%). Although PDL1-positivity was not significantly correlated with any clinical characteristics including age, sex, smoking/alcoholic history, stage, or differentiation, H-scores for c-Met expression were significantly associated with PDL1-positivity(OR = 2.34, 95%CI: 1.16-4.72, P = 0.017). PD-L1 expression was not significantly associated with a change in overall survival(P = 0.656). In contrast, the locoregional relapse rate tended to increase(P = 0.134), and the distant metastasis rate was significantly increased(HR = 1.72, 95%CI: 1.01-2.79, P = 0.028) in patients with PD-L1-positive ESCC compared to those with PD-L1-negative ESCC.CONCLUSION PD-L1 expression is positively correlated with c-Met expression in ESCC. PD-L1 may play a critical role in distant failure and progression of ESCC.     

Clinicopathological and prognostic role of cyclin D1 in esophageal squamous cell carcinoma: a meta-analysis

Cyclin D1 is one of the most commonly over-expressed oncogenes; however, its role in esophageal squamous cell carcinoma (ESCC) remains controversial. We conducted a meta-analysis of 20 studies, comprising 2,041 patients to clarify this issue. In all studies, paraffin-embedded surgical specimens were collected and the status of cyclin D1 was determined by immunohistochemistry (IHC). The combined odds ratios (Ors) for cyclin D1 expression were 0.74 (95% confidence interval [CI]: 0.58-0.93) for well and moderately differentiated versus poorly differentiated tumors, 0.65 (95% CI: 0.45-0.94) for T1/T2 versus T3/ T4 tumors, 0.59 (95% CI: 0.39-0.90) for N0 versus N1 tumors, and 0.48 (95% CI: 0.33-0.71) for stage I/II versus stage III/IV diseases, respectively. The association between cyclin D1 expression and prognosis was examined in 10 studies, and the combined hazard ratio was 1.78 (95% CI: 1.49-2.12). Cyclin D1 expression level detected by IHC is associated with worst clinicopathological features and prognosis for ESCC.     

Bcl—2基因蛋白在食管异型增生组织和鳞癌中的表达变化及其意义

目的：目前食管癌的主要诊断方法有赖于病理学，至今尚无特异性肿瘤标志物，为此对找辅助食管癌早期诊断的分子标志物进行研究。方法：采用单克隆抗体免疫组化LSAB方法检测了BCl－2基因在EM、EED和SCCE中表达变化及其意义。结果：EM组无异常表达；EED组阳性表达率为65．7％，与EM组相比差异有显著性（P＜0．05），在EED中BCl－2蛋白表达增加主要发生在2和3级EED中（P＜0．05）；在SCCE中阳性表达率为77．1％，与EED组相比差异无显著性（P＞0．05），Bcl－2蛋白过表达主要与高分化的SCCE有关（P＜0.05）。结论：食管癌早期发生阶段存在Bcl－2基因表达异常，早期检测Bcl－2基因表达变化可能有助于食管癌早期发生的评估；Bcl－2基因对食管癌的进展不起重要作用。     

食管鳞癌组织VCAM-1和Survivin的表达及意义

目的探讨血管细胞黏附分子1（VCAM-1）和Survivin与食管鳞癌细胞发生、发展与转移的关系。方法采用免疫组化法检测24例正常食管黏膜、94例食管鳞癌组织中Survivin和VCAM-1的表达情况。结果VCAM-1和Survivin在癌组织中的表达率明显高于正常食管黏膜,其中VCAM-1表达与淋巴结转移、浸润深度和临床分期等因素有关（P均〈0．05）;Survivin表达与浸润深度有关（P〈0．01）;VCAM-1和Survivin在癌组织中的表达无相关性。结论VCAM-1和Survivin在食管鳞癌中高表达,二者在食管鳞癌的发生、发展过程中具有重要作用,可作为评价食管鳞癌生物学行为的指标。     

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.     

Congenital expression of mdr-1 gene in tissues of carcinoma and its relation with pathomorphology and prognosis

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Expression of Bmi-1 and PAI-1 in esophageal squamous cell carcinoma

AIM:To determine the correlation between invasiveness,migration and prognosis in esophageal squamous cell carcinoma(ESCC)and expression of the B-cellspecific Moloney leukemia virus insert site 1(Bmi-1)and plasminogen activator inhibitor-1(PAI-1).METHODS:Eighty previously untreated patients who underwent surgical excision of ESCC were included.The expression of Bmi-1 and PAI-1 was examined immunohistochemically in formalin-fixed paraffinembedded primary tissue specimens.The relationships between the expression of Bmi-1 and PAI-1,the clinicopathologic features of ESCC,and the survival rate of ESCC patients were also discussed.The correlation between Bmi-1 and PAI-1 protein expression in ESCC was analyzed.The relationship between Bmi-1 and PAI-1expression and ESCC prognosis was evaluated using a Cox regression model and Kaplan-Meier survival curve analysis.RESULTS:The rates of positive Bmi-1 and PAI-1 expression in ESCC were higher than those in normal esophageal tissue(P<0.05).The expression of Bmi-1and PAI-1 was correlated with depth of invasion and lymph node metastasis(P<0.05),but not with patient age,tumor size or nationality(P>0.05).The expression of Bmi-1 was positively correlated with that of PAI-1(P<0.05).The 10-year overall survival rate for all patients was 20%(16∕80).Univariate KaplanMeier survival analysis showed that patients with high expression of esophageal PAI-1 and Bmi-1 had lower survival,however,the difference was not statistically significant.Cox multivariate analysis showed that PAI-1and Bmi-1 were not independent factors for survival rate,while the depth of tumor invasion and metastasis were independent factors affecting patient survival.CONCLUSION:The expression of Bmi-1 and PAI-1plays a role in ESCC progression,and may be used as a prognostic marker in ESCC.     

食管癌组织MCM2的表达及意义

目的探讨MCM2作为细胞新增殖指标的可靠性及其对判断食管鳞癌预后的意义。方法采用免疫组化法检测134例食管鳞癌组织中MCM2及增殖细胞核抗原（PCNA）的表达．分析它们的相关性及与食管鳞癌分化、分期和预后的关系。结果MCM2的表达强弱与食管癌的分化程度密切相关。分化越低,表达越明显（P〈0．01）;表达强弱与食管癌的临床分期无关。MCM2与PCNA呈显著正相关（r=0．701,P〈0．01）。COX回归模型显示肿瘤分期、MCM2为独立的预后指标。结论MCM2可作为判断食管鳞癌增殖速率和预后的独立指标,其高表达提示预后不良。     

Routine endoscopic screening for synchronous esophageal neoplasm in patients with head and neck squamous cell carcinoma: a prospective study

Early detection of synchronous esophageal squamous cell neoplasm (ESCN) in head and neck squamous cell carcinoma (HNSCC) patients can significantly affect their prognosis. We investigated the prevalence of synchronous ESCN and the risk factors for developing ESCN in patients with HNSCC, and evaluated the effect of routine endoscopic screening in these patients. Subjects who were diagnosed as HNSCC from May 2010 to January 2014 were eligible. All patients underwent conventional white light endoscopic examinations with narrow band imaging and Lugol chromoendoscopy. Among 458 subjects screened, 28 synchronous ESCN were detected in 24 patients (5.2%). The prevalence of ESCN was greatest in patients with hypopharyngeal cancer (20.9%). In multivariate analysis, pyriform sinus involvement was independent risk factor for developing synchronous ESCN (odds ratio 171.2, P < 0.001). During the follow‐up period (median, 24 months), the 3‐year overall survival rates was significantly lower in patients with ESCN than in patients without ESCN (54.2% vs. 78.3%, P = 0.0013). Routine endoscopic screening for detecting synchronous ESCN should be recommended for patients with HNSCC, especially those with pyriform sinus involvement.