食管鳞癌患者血清中VEGF的表达变化及意义

目的观察食管鳞癌患者血清血管内皮生长因子（VEGF）的表达变化,并探讨其意义。方法采用ELISA法检测46例食管鳞癌患者和10名健康体检者外周静脉血血清中的VEGF。结果食管癌患者血清VEGF水平为（502.176±65.218）pg/ml,对照组为（311.648±40.984）pg/ml,两组相比,P〈0.01;根据肿瘤国际TNM分期标准：食管癌组Ⅰ期＋Ⅱ期者血清VEGF水平为（446.890±50.602）pg/ml,Ⅲ期者为（580.012±56.996）pg/ml,两组相比,P〈0.01;浸润深度T1＋T2者血清VEGF水平为（434.725±49.703）pg/ml,T3者为（503.504±68.500）pg/ml、T4者为（595.441±48.192）pg/ml,三者相比,P均〈0.01;有淋巴结转移者血清VEGF水平为（576.011±61.798）pg/ml,高于无淋巴结转移者的（464.340±68.639）pg/ml,P〈0.01。结论食管鳞癌患者血清VEGF表达升高,与肿瘤的发生、浸润深度、淋巴结转移情况及TNM分期相关。VEGF是食管鳞癌发生发展预后判断的一个有价值的依据。     

食管鳞癌组织中hMLH1 mRNA的表达变化及意义

目的观察食管鳞癌组织中错配修复基因hMLH1 mRNA的表达变化,并探讨其临床意义。方法采用RT-PCR法检测60例食管鳞癌组织与癌旁组织中的hMLH1 mRNA。结果食管鳞癌组织中hMLH1 mRNA相对表达量（0.761 7±0.035 7）明显低于癌旁正常组织（1.025 2±0.047 4）,P〈0.05;hMLH1 mRNA的相对表达量与食管鳞癌分化程度、肿瘤浸润深度和淋巴结转移无关（P均〉0.05）,与病理分期有关（P〈0.05）。结论hMLH1 mR-NA表达缺失参与了食管鳞癌的发生或发展。     

食管鳞癌组织中PLK1表达变化及其对食管癌细胞侵袭迁移的影响

目的观察食管鳞癌组织中Polo样激酶1(PLK1)的表达变化,及其对食管癌细胞侵袭迁移能力的影响。方法采用免疫组化SP法检测80例食管鳞癌及癌旁组织中的PLK1,分析其与食管鳞癌临床病理参数及患者生存期的关系。将对数生长期的人食管癌EC9706细胞分为两组,观察组转染PLK1 siRNA,对照组转染ScrambledsiRNA;用Transwell小室观察两组食管癌细胞侵袭及迁移能力,Western blot法检测两组食管癌细胞中的PLK1、MMP-2、MMP-9。结果食管鳞癌组织中PLK1阳性表达53例(66.3%),癌旁组织中PLK1阳性表达27例(33.7%);两者比较,P<0.05。PLK1表达与食管鳞癌淋巴结转移及临床分期有关(P均<0.05)。PLK1阴性者5年生存率为62%,高于PLK1阳性者的39%(P<0.05)。多因素Cox回归分析显示,临床分期、淋巴结转移、病理分级、PLK1表达均为食管癌预后的独立危险因素。观察组EC9706侵袭迁移个数分别为(120±6)、(269±8)个/HP,对照组分别为(468±11)、(780±12)个/HP;两组比较,P均<0.05。观察组EC9706中PLK1、MMP-2、MMP-9灰度比值分别为0.1±0.03、0.40±0.02、0.87±0.05,对照组分别为0.96±0.05、0.98±0.07、0.89±0.06;两组PLK1、MMP-2灰度比值比较,P均<0.05。结论食管鳞癌组织中PLK1表达增加,其在食管鳞癌的发生发展中起重要作用;敲降PLK1表达可降低食管癌细胞的侵袭迁移能力,该作用与MMP-2的表达下调有关。     

MTSS1及Gli1在食管鳞癌组织中表达及其相关性

目的 检测食管鳞癌组织中肿瘤转移抑制蛋白(MTSS)1及胶质瘤相关癌基因蛋白(Gli)1的表达水平,探讨MTSS1和Gli1的相关性。方法 应用免疫组织化学SP法和原位杂交方法检测136例食管鳞癌组织及其相应的96例癌旁不典型增生组织和136例正常食管黏膜组织中MTSS1、Gli1蛋白及mRNA的表达水平。结果 MTSS1蛋白和mRNA在食管鳞癌组织中的阳性表达率显著低于癌旁组织和正常食管黏膜组织,两两比较差异均有统计学意义(P<0.05)。Gli1蛋白和mRNA在食管癌组织中的阳性表达率显著高于癌旁不典型增生组织和正常食管黏膜组织,两两比较差异均有统计学意义(P<0.05)。有淋巴结转移组食管鳞癌组织中MTSS1蛋白及mRNA阳性表达率均显著低于无淋巴结转移组(P<0.05);有淋巴结转移组食管鳞癌组织中Gli1蛋白及mRNA阳性表达率均显著高于无淋巴结转移组(P<0.05);Gli1和MTSS1蛋白在食管鳞状上皮细胞癌组织中的表达呈负向相关(r=-0.422,P<0.05),Gli1和MTSS1 mRNA在食管鳞状上皮细胞癌组织中的表达亦呈负向相关(r...     

下咽鳞癌组织中Paxillin mRNA的表达变化及意义

目的观察下咽鳞癌组织中桩蛋白（Paxillin）mRNA的表达变化,并探讨其临床意义。方法采用荧光定量RT-PCR法检测38例下咽鳞癌患者癌组织及癌旁组织中的Paxillin mRNA。结果下咽癌组织中Paxillin mRNA表达量为12 871.5,正常组织中为3 405.0,两者比较,P〈0.05。下咽癌组织中,低、中、高分化者Paxillin mRNA表达量分别为17 163.0、11 333.5、6 760.5,三者比较,P〉0.05;浸润程度浅者为7 821.0,深者为16 783.0,两者比较,P〈0.05;有淋巴结转移者为19 832.0,无转移者为6 721.0,两者比较,P〈0.05。结论下咽鳞癌组织中Paxil-lin mRNA表达增加,Paxillin与下咽癌的发生发展有关。     

nm23蛋白检测对食管鳞癌淋巴结转移的预测价值

采用免疫组织化学方法检测８５例食管鳞癌ｎｍ２３蛋白表达。结果３４例（４０％）呈ｎｍ２３阴性。ｎｍ２３阴性表达与肿瘤的浸润深度、淋巴结转移和ＴＮＭ分期有关（Ｐ＝０．０１,Ｐ＝０．００１和Ｐ＝０．００１）,ｎｍ２３低表达表达者相经,淋巴结转移的风险比例（ＯＲ值）为７２．１８７。因此认为,对原发瘤或活检组织ｎｍ２３的免疫组化检测有可能成为评价食管鳞癌肿瘤分期及淋巴结转移的一个有价值的预测指标。     

食管鳞癌clusterin表达及其临床意义

目的:探讨食管鳞癌组织clusterin表达和单纯手术治疗前后外周血clusterin含量变化与食管鳞癌临床参数的相关性.方法:RT-PCR分析5对食管鳞癌及其远端切缘食管上皮中clusterin基mRNA表达水平;ELISA分析41例单纯手术治疗食管鳞癌患者治疗前后的血清clusterin蛋白表达水平及其与临床特征的相关性.结果:与正常食管上皮相比食管鳞癌组织中clusterin基因表达显著下降或缺失.食管鳞癌患者术前血清中clusterin含量明显低于术后血清含量(3.23 mg/Lvs 25.71 mg/L,P<0.0001).食管鳞癌患者术前血清clusterin含量与肿瘤大小相关(P<0.01),而与年龄、性别、分化程度、肿瘤分期、淋巴结转移.以及总蛋白、白蛋白、血糖、血脂和总胆红素浓度无关(r=-0.1334,-0.1602,0.2413,0.0389,-0.2882,均p>0.05).结论:clusterin基因在食管鳞癌组织中表达明显下调或缺失,血清clusterin含量明显降低,提示在食管鳞状细胞癌中clusterin基因可能具有潜在的抑癌基因作用,动态检测外周血clusterin含量有助于判断食管癌进展.     

BAG-1在食管鳞癌组织中的表达及意义

采用免疫组化S-P法检测92份食管鳞癌组织和20份正常食管黏膜中抗凋亡基因BAG-1的表达,并采用TNUEL法检测细胞凋亡指数。结果食管鳞癌组织BAG-1阳性表达率为70．6％（65／92）,明显高于正常食管黏膜组织15％（3／20）,差异有统计学意义BAG-1表达与癌组织分化程度、TNM分期、淋巴结转移密切相关;随BAG-1表达强度的增加,癌细胞凋亡指数逐渐降低。认为BAG-1能抑制癌细胞调亡,其表达与食管鳞癌的发生、发展密切相关,可作为食管鳞癌治疗的新靶点。     

食管鳞癌组织中胸苷磷酸化酶表达变化及意义

目的 观察食管鳞状细胞癌（ESCC）组织中胸苷磷酸化酶（TP）的表达变化,并探讨其与微血管密度（MVD）、细胞凋亡的关系.方法 采用免疫组化法检测155例ESCC患者肿瘤组织及癌旁组织中的TP、CD34以及ssDNA,CD34标记计数MVD,ssDNA阳性计算肿瘤细胞的凋亡指数（AI）.结果 155例ESCC患者中,肿瘤细胞TP表达阳性89例（57.4％）,基质细胞TP表达阳性104例（67.1％）；癌组织中平均MVD值为365条/mm2,其癌旁正常组织中平均MVD值为222条/mm,P＜0.01.155例中有154例（99.4％）检出凋亡阳性,AI均值为2.1％,二者无明显的相关性（P =0.074 7）.基质细胞TP阳性者MVD值明显高于TP阴性者（P＜0.01）,但肿瘤细胞TP是否阳性与MVD值无明显的关系；肿瘤细胞TP阳性者AI明显低于TP阴性者（P＜0.01）,基质细胞TP阳性者AI也低于TP阴性者,但差异并不显著.155例ESCC患者5年总生存率为32.5％.单因素分析显示,TNM分期越高、肿瘤细胞TP阳性、AI低是ESCC患者预后不佳的因素；多因素分析结果显示,TNM分期是ESCC独立预后评估因素.结论 TP可能通过增加微血管的生成及抑制肿瘤细胞凋亡等途径,在ESCC进展过程中起重要作用.     

食管鳞癌组织中HIF-lα、Caspase-3蛋白的表达变化及意义

目的探讨食管鳞癌组织中缺氧诱导因子（HIF）-1α、半胱氨酸天冬氨酸蛋白酶（Caspase）-3蛋白的表达变化及其与肿瘤浸润、转移的关系。方法应用免疫组化SP法检测49例食管鳞癌中HIF-1,αCaspase-3蛋白的表达。结果食管鳞癌组织中HIF-1α、Caspase-3蛋白阳性表达率分别为51.0%（25/49）、34.7%（17/49）,与阴性对照组的0、100%相比,P均〈0.05。HIF-1α、Caspase-3蛋白表达与食管鳞癌组织浸润深度及有无淋巴结转移有关（P均〈0.05）,与分化程度无关（P〉0.05）。HIF-1α、Caspase-3蛋白在食管鳞癌中的表达呈负相关（P〈0.05）。结论食管鳞癌组织中存在HIF-1α蛋白的高表达和Caspase-3蛋白的缺失或低表达。这一变化与食管鳞癌的浸润转移有关,其机制可能与HIF-1α蛋白下调Caspase-3蛋白的表达有关。     

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.     

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。     

胸段食管鳞癌淋巴结转移规律及淋巴结清扫方式探讨

目的探讨胸段食管鳞癌淋巴结转移规律及术中淋巴结清扫方式。方法 480例行根治术的胸段食管鳞癌患者,标记各部位清扫淋巴结分别送检,进行临床病理资料分析。结果本组386例患者有淋巴结转移。全组清扫淋巴结5 424枚,平均每例清扫11.3枚,689枚淋巴结有转移。22例患者出现跳跃性淋巴结转移,其中胸上段3例、中段9例、下段1例。胸上段食管鳞癌颈部淋巴结转移率47.6%,高于胸中段（10.5%）和胸下段（1.3%）,P均〈0.05。胸下段食管鳞癌向腹腔淋巴结转移率为33.1%,高于胸中段（19.4%）和胸上段（3.8%）,P均〈0.05。胸中段食管鳞癌有上纵隔淋巴结（23.5%）及下纵隔淋巴结（29%）和腹腔淋巴结（19.4%）的双向转移趋势,隆突下淋巴结转移多见,转移率54.2%。结论 胸上段食管癌淋巴结转移以颈段食管旁、锁骨上、上中纵隔转移多见,胸中段食管癌淋巴结转移具有明显的上下双向转移和跳跃性转移特点,胸下段食管癌淋巴结转移以腹部、中下纵隔转移多见。胸上段食管癌行颈、胸、腹三野淋巴结清扫,重点清扫颈段食管旁及锁骨上、下界包括隆突下淋巴结;胸下段食管癌可行胸、腹两野淋巴结清扫,重点清扫隆突下、下胸段食管旁、胃左动脉旁淋巴结;胸中段食管癌淋巴结清扫方式应根据具体情况设定。     

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.     

Clinicopathologic factors predicting lymph node metastasis in superficial esophageal squamous cell carcinoma

Abstract

Objective. Surgical resection is the treatment of choice for superficial esophageal squamous cell carcinoma (SESCC), but it is associated with high mortality and morbidity rates. Recently, endoscopic resection for SESCC has been indicated for patients with a low risk of lymph node metastasis (LNM). Therefore, to successfully treat SESCC with endoscopic resection, it is very important to identify patients with a low risk for LNM. The objective of this study was to investigate clinicopathologic factors that predict LNM in patients who underwent esophagectomy for SESCC. Methods. The study included 104 patients with SESCC from three university hospitals in Pusan, Korea. Clinicopathologic factors were evaluated to identify independent factors predicting LNM by univariate and multivariate analyses. Results. In univariate analysis, the depth of tumor invasion and lymphovascular invasion had significant influences on LNM (p = 0.001 and p < 0.001, respectively). Gross type, tumor size, and tumor differentiation were not predictive for LNM. In multivariate analysis, the depth of tumor invasion and lymphovascular invasion were signi?cantly associated with LNM in patients with SESCC (OR 9.04, p = 0.049; OR 11.61, p = 0.002, respectively). Conclusions. The depth of tumor invasion and lymphovascular invasion were independent predictors of LNM in patients with SESCC. Therefore, endoscopic resection could be performed in patients with SESCC that is limited to the mucosa, without lymphovascular invasion.     

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。     

Paraesophageal lymph node metastasis from prostatic adenocarcinoma in a patient with esophageal squamous carcinoma

SUMMARY. Esophageal squamous carcinomas induce regional immune suppression in the domain of the tumor while the global immune system remains intact. We report a patient with a squamous esophageal carcinoma, who was discovered at esophagectomy to have paraesophageal lymph node metastases from a prostatic adenocarcinoma. No other sites of metastatic disease were identified. This supports the concept that regional immune suppression by esophageal squamous cancers facilitates growth of metastases in the local lymph nodes.     

Tumor cell dissociation score highly correlates with lymph node metastasis in superficial esophageal carcinoma

BACKGROUND: It is still not clear which parameters are important for predicting the metastatic potential of superficial esophageal squamous cell carcinoma (SESCC). The purpose of the present paper was thus to investigate tumor cell dissociation (TCD) in SESCC as a predictive factor of lymph node metastasis. METHODS: Thirty-three SESCC were classified into four groups based on the depth of tumor invasion. Carcinomas not invading as far as the muscularis mucosa were classified as group A; carcinomas invading to the muscularis mucosa or less than one-third of the upper submucosa were classified as group B; those invading to the middle layer of the submucosa were classified as group C; and those invading one-third of the lower submucosa were classified as group D. The TCD score was calculated by dividing the length of the TCD region by the maximal longitudinal length of the area of invasion into or beyond the lamina propria, and multiplying by 100. E-cadherin expression of the carcinomas was investigated in the TCD area and the successive area of mucosal invasive carcinoma (SAM). RESULTS: The incidence of lymph node metastasis was 0% in group A, 10% in group B, 36.4% in group C and 57.1% in group D. The mean TCD scores (+/-SEM) of SESCC with lymph node metastasis were higher than that without (85.3 +/- 5.7, 16.3 +/- 3.9, respectively; P < 0.001). In group C, the TCD score of cases with lymph node metastases was higher than in those without lymph node metastasis (P < 0.001). E-cadherin expression was significantly reduced in the area of TCD compared with the SAM located over the TCD area (P < 0.001). CONCLUSIONS: The TCD score is an important predictive marker for lymph node metastasis in SESCC. Clinical evaluation of TCD scores in endoscopic mucosal resection (EMR) specimens would enable accurate prediction of lymph node metastasis and extend the indication of EMR treatment for SESCC.     

Study of abnormal chromosome regions in esophageal squamous cell carcinoma by comparative genomic hybridization: relationship of lymph node metastasis and distant metastasis to selected abnormal regions

Squamous cell carcinoma of the esophagus (ESCC) has a poor prognosis among digestive tract cancers. Lymph node metastasis and distant metastasis are the major factors determining its prognosis. We used comparative genomic hybridization (CGH) to evaluate primary tumor lymph nodes and metastatic areas from ESCC patients in order to determine the relationship between abnormal chromosome regions and outcome. Tumor tissues and lymph nodes were collected from 51 patients with ESCC, and abnormal chromosome regions were detected by CGH. We searched for regions that were significantly more common in patients with lymph nodes metastases (n≥ 6) or distant metastases, and correlated those chromosomal changes with survival. Regions showing amplification in more than 65% of esophageal squamous cell cancers were as follows: 17q12 (90.2%), 17q21 (86.3%), 3q29 (82.4%), 3q28 (78.4%), 8q24.2 (76.5%), 22q12 (76.5%), 3q27 (74.5%), 8q24.3 (74.5%), 1q22 (70.6%), 5p15.3 (70.6%), 22q13 (70.6%), 3q26.3, 8q23, 8q24.1, 9q34, 11q13, 17p12, 17q25, 20q12, 20q13.1 (68.6%), 1q32, 1q42, and 20q13.2 (66.7%). Regions showing deletion in more than 50% of the tumors were as follows: Yp11.3 (62.7%), 3p26 (56.9%), Yq12 (54.9%), 13q21 (52.9%), 4q32 (51.0%), and 13q22 (51.0%). When Fisher's test was used to assess associations of these regions with metastases to lymph nodes, amplification at 2q12–14 (P= 0.012), 3q24–26 (P= 0.005), and 7q21–31 (P= 0.026) were significant. Survival was worse for patients with amplification at all 3 regions. In patients with distant organ metastases, amplification at 7p13–21 was significant (P= 0.008), and survival was worse. Chromosomal amplifications in ESCC at 2q12–14, 3q24–26, and 7q21–31 were associated with lymph node metastasis, while amplification at 7p13–21 was related to distant metastasis. Amplification at these regions correlated with worse survival. Genes involved in the phenotype of ESCC may exist in these regions. Identification of these genes is a theme for future investigation.