Histone demethylase GASC1, a potential prognostic and predictive marker in esophageal squamous cell carcinoma

Gene amplified in squamous cell carcinoma 1 (GASC1) is a member of Jumonji C-domain containing histone demethylases that play an essential role in affecting chromatin architecture and gene expression. The purpose of this study was to determine the expression features and the clinical significance of GASC1 in esophageal squamous cell carcinoma (ESCC). GASC1 expression was detected on tissue microarrays of ESCC samples in 185 cases using immunohistochemical staining. Strong nuclear staining for GASC1 was observed in a subset of ESCC samples. The nuclear expression of GASC1 was significantly associated with lymph node metastasis (P=0.030) and tumor-node metastasis stages (P=0.013). Kaplan-Meier survival analysis showed a tendency that high expression of GASC1 in the nucleus was associated with poor survival of ESCC patients, with a 5-year survival rate of 26.5%, as compared to 43.7% for patients with GASC1-negative/low expression. Furthermore, multivariate analysis revealed that high expression of GASC1 likely acts as a predictive factor for overall survival of ESCC patients, despite the P-value failing to reach significance (P=0.059). The findings indicate that histone demethylase GASC1 may play an important role in promoting cancer metastasis, and shed new light on the importance of targeting GASC1 to suppress metastatic disease in various tumor types, including ESCC.     

Silver stained nucleolar organizer region proteins and Helix pomatia agglutinin immunostaining in esophageal carcinoma: Correlated prognostic factors

The number of nucleolar organizer region proteins identified by silver staining (AgNORs) and alterations in cell surface glycoproteins identified by Helix pomatia agglutinin (HPA) immunostaining were studied in 96 primary esophageal carcinomas. The number of AgNORs increased with increasing depth of cancer invasion, venous involvement, lymphatic invasion, and tumor stage. Positivity of HPA staining correlated significantly with increasing depth of cancer invasion, venous invasion, and tumor stage. Forty of 42 HPA negative cases had low AgNORs numbers (<4), while 39 of 54 HPA positive cases had high AgNORs numbers (?4) (P = 0.0001). The survival rate of patients with stage III and IV disease was significantly poorer for those with a high AgNORs score and HPA positivity than in those with a low AgNORs score and HPA negativity. The present study indicates that the AgNORs score is positively correlated with positive HPA staining and that tumors having both factors represent a subgroup of esophageal carcinomas with poor prognosis. © 1994 Wiley-Liss, Inc.     

50例新疆维吾尔族食管鳞癌组织中survivin、p53蛋白的表达及临床意义

目的:探讨survivin、p53蛋白在维吾尔族食管鳞癌组织中的表达及其与临床病理指标的相关性,并进一步探讨其在食管鳞癌发生、发展中的作用.方法:应用免疫组织化学法(EnVision二步法),检测survivin和p53蛋白在50例食管鳞癌组织及18例食管正常切缘组织中的表达情况.结果:50例食管鳞癌中survivin和p53基因的阳性表达率为66％和38％,明显高于对照组(食管正常切缘组织)(P＜0.05).survivin、p53蛋白在中晚期食管癌中的阳性表达与食管癌的分期、分化程度相关(P＜0.05),而与食管鳞癌患者的年龄、性别、肿瘤大小、浸润深度、有无淋巴结转移无关(P＞0.05).survivin与p53蛋白在食管鳞癌中的表达无显著相关(r =0.040,P＞0.05).结论:survivin、p53蛋白在食管鳞癌组织中的表达明显高于食管正常组织.表达的高低与食管鳞癌临床分期、病理分化程度有关,有助于判断食管鳞癌的恶性程度及临床预后.     

食管鳞状细胞癌预后的多因素分析

目的:通过对食管鳞状细胞癌(ESCC)多个临床病理因素进行分析,探讨影响其预后的因素。方法:对1986-2002年接受根治性手术治疗的1325例ESCC患者的预后进行回顾性研究。选取性别、年龄、肿瘤长径、分化程度、浸润深度、淋巴结转移和临床分期7个可能对ESCC患者预后有影响的指标,通过Kaplan-Meier生存分析及Cox比例风险模型进行单因素及多因素分析,筛选出影响ESCC患者预后的因素。结果:1 325例ESCC患者术后1、3、5和10年累计生存率分别为72.0%、53.0%、41.0%和1.06%。Kaplan-Meier单因素生存分析结果显示,不同肿瘤长径、分化程度、浸润深度、淋巴结转移和临床分期的ESCC患者5年生存率差异有统计学意义,P<0.01;淋巴结转移阳性组5年生存率为19.4%明显低于淋巴结转移阴性组的50.2%。肿瘤长径大、分化程度低、肿瘤浸润深度深、临床分期晚和有淋巴结转移患者其5年生存率低,预后差。COX多因素分析亦表明分化程度、浸润深度、淋巴结转移和临床分期是影响ESCC预后的相关因素P<0.01。而不同年龄和性别患者5年生存率差异无统计学意义,P>0.05。结论:肿瘤浸润深度、分化程度、淋巴结转移和临床分期可能是判断ESCC预后的独立指标。     

Clinical significance of mannose-binding lectin-associated serine protease-2 expression in esophageal squamous cell carcinoma

Mannan-binding lectin-associated serine protease-2 (MASP-2) is a serine protease involved in the activation of lectin complement pathway. The differential expression of MASP-2 in human esophageal squamous cell carcinoma (ESCC) was recently reported from our laboratory using differential display. To determine the expression of MASP-2 protein, we raised a polyclonal antibody to human MASP-2 and used it for immunohistochemical analysis of MASP-2 in ESCCs. The antibody showed a single band of predicted molecular weight by western blotting. In normal human liver tissue, the cytoplasm was distinctly labeled by the antibody. Intriguingly, besides the cytoplasm, the nuclei of esophageal tumor cells were also labeled. To investigate the association of MASP-2 expression with esophageal tumorigenesis, its expression was analyzed in 51 primary ESCCs, 32 dysplasias, 21 histologically normal esophageal tissues and 6 adenocarcinomas by immunohistochemistry. Increased MASP-2 expression was observed in ESCCs (p = 0.001, Odd's ratio (OR) = 3.662) and in premalignant condition, dysplasia (p = 0.000, OR = 5.091) in comparison with the normal tissues. MASP-2 expression in ESCCs was associated with late clinical stage (p = 0.009, O.R. = 3.430) and nodal metastasis (p = 0.001, O.R. = 4.520). In conclusion, our antibody was demonstrated to be useful in recognizing MASP-2 expression on paraffin embedded tissue sections. To our knowledge, this is the first report showing MASP-2 expression in a solid tumor. MASP-2 expression in premalignant stage (dysplasia) as well as in ESCCs and its association with late clinical stage and nodal metastasis suggest that alteration in its expression is maintained during disease progression and is associated with aggressive tumor behavior.     

A nomogram to predict prognostic values of various inflammatory biomarkers in patients with esophageal squamous cell carcinoma

Background: Inflammation plays an important role in cancer progression and prognosis. However, the prognostic values of inflammatory biomarkers in esophageal cancer (EC) were not established. In the present study, therefore, we initially used a nomogram to predict prognostic values of various inflammatory biomarkers in patients with esophageal squamous cell carcinoma (ESCC). Methods: A total of 326 ESCC patients were included in this retrospective study. Glasgow prognostic score (GPS), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and lymphocyte monocyte ratio (LMR) were analyzed in the current study. Kaplan-Meier method was used to calculate the cancer-specific survival (CSS). Cox regression analysis was also performed to evaluate the prognostic factors. A nomogram was established to predict the prognosis for CSS. Results: Patients were divided into 3 groups according to GPS (GPS 0, 1 and 2) and 2 groups according to NLR (≤3.45 and >3.45), PLR (≤166.5 and >166.5) and LMR (≤2.30 and >2.30). The 5-year CSS in patients with GPS 0, 1 and 2 were 49.2%, 26.8% and 11.9%, respectively (P<0.001). In addition, patients with NLR (>3.45), PLR (>166.5) and LMR (≤2.30) were significantly associated with decreased CSS, respectively (P<0.001). Multivariate analysis revealed that GPS (P<0.001), PLR (P=0.002) and LMR (P=0.002) were independent prognostic factors in patients with ESCC. In addition, a nomogram was established according to all significantly independent factors for CSS. The Harrell’s c-index for CSS prediction was 0.72. Conclusion: GPS, PLR and LMR were potential prognostic biomarkers in patients with ESCC. The nomogram based on CSS could be used as an accurately prognostic prediction for patients with ESCC.     

食管鳞状细胞癌组织中Survivin和Cox-2及PCNA表达临床意义的研究

目的探讨Survivin、Cox-2和PCNA表达与食管鳞状细胞癌（esophageal squamous cell carcinoma,ESCC）临床病理因素及相互之间的关系。方法应用免疫组织化学（SP）方法检测Survivin、Cox-2蛋白和增殖细胞核抗原在51例食管鳞癌和30例切缘正常食管黏膜中的表达。结果Survivin和Cox-2在食管鳞癌的表达均高于切缘正常食管黏膜,P〈0.01。Survivin蛋白在食管鳞癌组织中的表达阳性率与肿瘤分化程度相关,P〈0.05。Cox-2蛋白的表达阳性率与食管鳞癌的临床病理特征无关,P〉0.05。PCNA的表达阳性率与食管鳞癌的分化程度、淋巴结转移有关,差异有统计学意义,P〈0.05。51例食管鳞癌组织中Survivin与Cox-2、PCNA之间具有显著正相关性,P〈0.01;Survivin与PCNALI（反映细胞增殖活性的指标）具有正相关性,P〈0.05;Cox-2与PCNA之间无相关性,P〉0.05。结论Survivin与COX-2蛋白在食管鳞癌组织中均有较高的阳性表达,两者表达具有相关性,两者可能存在共同的激活机制,构成抑制食管鳞癌细胞凋亡的多种途径。Survivin表达与食管鳞癌的恶性进程有关。     

食管鳞癌组织Nanog表达临床意义分析

目的研究食管鳞癌组织中Nanog蛋白表达情况及其与食管癌患者预后的相关性。方法收集河北北方学院附属第一医院2000-01-01-2005-12-31手术切除的食管癌存档标本蜡块69例及正常食管黏膜组织（距肿瘤组织〉5cm）24例,应用免疫组化SP法检测食管鳞癌及癌旁正常黏膜组织中Nanog的表达,分析其与各临床病理因素的相关性;结合Nanog的表达情况及随访资料,Kaplan-Meier法和Log-rank检验分析Nanog与食管癌患者生存的相关性;并建立Cox回归模型评估Nanog及各临床病理因素与患者预后的相关性。结果食管鳞癌组织中Nanog表达阳性率为40.6%（28/69）,显著高于正常组织的8.3%（2/24）,χ^2=8.473,P=0.004。Nanog的表达与组织分化程度（χ^2=7.137,P=0.008）、淋巴结转移（χ^2=4.947,P=0.026）、外膜浸润（χ^2=11.110,P=0.001）和UICC分期（χ^2=5.301,P=0.021）明显相关,而与患者年龄（χ^2=0.238,P=0.626）和性别（χ^2=1.229,P=0.268）无相关性;死亡患者Nanog的表达程度为49.0%（25/51）,明显高于生存患者的16.7%（3/18）,χ^2=5.775,P=0.016;Nanog表达水平与食管癌患者预后明显相关,RR=1.913,P=0.002。结论 Nanog在食管鳞癌组织中呈高表达,与患者生存期相关,Nanog是影响食管癌患者预后的独立因素。     

Expression of RCAS1 in esophageal squamous cell carcinoma is associated with a poor prognosis

BACKGROUND: Receptor-binding cancer antigen expressed on SiSO cells (RCAS1) has been reported to act as a ligand for a receptor present on normal peripheral lymphocytes and to induce apoptotic cell death. We aimed to elucidate the significance of RCAS1 expression in human esophageal squamous cell carcinomas (ESCC). METHODS: RCAS1 expression was examined immunohistochemically in surgically resected esophageal carcinoma tissues from 114 patients. We also examined the relationships between RCAS1 expressions, the tumor Ki-67 indices (a marker of proliferation), and the number of CD8+ tumor-infiltrating lymphocytes (TILs). RESULTS: RCAS1 immunoreactivity was detected in the membranes and cytoplasm of the tumor cells. Of the 114 esophageal carcinomas, 39 (34.2%) were strongly positive for RCAS1 immunostaining on the membranes of the cancer cells, 41 (36.0%) were weakly positive, and 34 (29.8%) were negative. A comparison of RCAS1 expression and clinicopathological characteristics in all 114 patients revealed significant associations between RCAS1 expression and lymph node status (P < 0.05), and pathologic stage (P < 0.05). The survival rates of patients with RCAS1-negative tumors were significantly higher than those of patients with both RCAS1-weak positive tumors and RCAS1-strong positive ones (log-rank P < 0.05). Multivariate analysis revealed that RCAS1 positivity was an independent prognostic factor (P < 0.05). The relationship between RCAS1 expression and the numbers of CD8+ T-cells in the primary tumors revealed that RCAS1-negative tumors tended to contain more of these cells than both RCAS1-weak positive tumors and RCAS1-strong positive ones (P = 0.2495). CONCLUSIONS: RCAS1 may play a significant role in tumor progression via an immune escape mechanism; thus, RCAS1 expression could be used as a predictor of poor prognosis in patients with ESCC.     

CtBP2 在食管鳞状细胞癌中的表达及其临床意义*

目的：研究羧基末端结合蛋白2（C-terminal binding protein 2,CtBP2）在食管鳞状细胞癌组织中的表达情况及其与食管癌发生发展的关系。方法：Westernblot法检测8 对食管鳞状细胞癌新鲜冰冻组织、免疫组化法检测90例食管鳞状细胞癌石蜡切片组织中CtBP2 表达情况,结合临床病理和随访资料分析CtBP2 表达与患者临床病理参数及总生存率的关系。结果：两法检测结果均显示CtBP2 食管鳞状细胞癌组织中的表达明显高于对应的癌旁组织,且CtBP2 的表达水平与食管癌的组织学分级（P =0.002）、浸润深度（P = 0.032）相关,而与年龄、性别等参数无相关性。Kaplan-Meier 分析结果显示,CtBP2 高表达组患者的总体生存率明显低于CtBP2 低表达组患者。结论：CtBP2 在食管鳞状细胞癌组织中表达显著上调,提示其可能与食管鳞状细胞癌的发生发展相关。     

Univariate and multivariate analyses of the prognostic significance of discontinuous intramural metastasis in patients with esophageal cancer

A review of 167 cases of esophageal carcinoma without preoperative treatment revealed 24 (14.4%) to have intramural metastasis (IM) within the esophagus. Among the clinicopathologic factors, the length of the lesions (P < 0.01), lymph node metastasis (P < 0.001), and the depth of the invasion of the tumor (P < 0.0001) were found to be statistically significant different factors between the two groups of patients both with and without intramural metastasis. The survival curve for patients with IM was significantly lower than that for patients without IM (P < 0.0001). A univariate analysis revealed that the depth of invasion, lymph node metastasis, IM (P < 0.0001), and the length of the lesion (P < 0.001) all had a significant correlation with the prognosis. Moreover, in a multivariate analysis, the depth of the invasion (<0.001), length of the lesion (0.001), and IM (0.049) were all determined to be significant prognostic factors. Therefore, IM is considered to be one of the independent significant prognostic factors for predicting a poor prognosis in esophageal cancer. © 1994 Wiley-Liss, Inc.     

Survivin expression in oral squamous cell carcinoma

A series of 110 cases of oral squamous cell carcinoma (SCC) together with six lymph node and one distant metastatic lesions was analysed for expression of survivin, a recent apoptosis inhibitor, by immunohistochemistry and Western blotting. In total, 91 cases (82.7%) of carcinoma and all metastasis (seven cases, 100%) were positive for survivin expression, with weighted survivin scores ranging from 1 to 4. In contrast, normal oral epithelium did not express survivin. There was no significant correlation between survivin expression and age, sex, tumour size, the presence of lymph node and distant metastases. Survivin expression was increased in poorly differentiated tumours, even if differences were not statistically significant. In contrast, when analysed for prognostic significance, patients with low survivin expression had statistically significant better survival rates than the group with high survivin expression (P<0.05). These data suggest that survivin expression may identify cases of oral SCC with more aggressive and invasive phenotype.     

No期食管鳞癌根治术后预后因素的Cox回归分析

目的：探讨No期食管鳞癌术后生存率的影响因素。方法：选择10个可能对术后预后产生影响的研究因素，通过Cox比例风险模型进行多因素分析，对我院1998年8月～2001年8月间的98例No期食管鳞癌术后患者预后进行研究。结果：全组1、3、5年生存率分别为95．92％、85．71％、81．63％。结论：Cox多因素分析显示，影响预后的独立因素是肿瘤浸润深度（T分期），肿瘤分化分级。     

Survivin在食管鳞癌组织中的表达及其意义

目的：探讨Survivin在食管鳞癌中的表达及其临床意义。方法：采用免疫组织化学检测47例食管鳞癌组织和10例正常食管黏膜的Survivin蛋白的表达，探讨其与食管鳞癌临床病理特征及预后之间的关系。结果：Survivin阳性表达定位于肿瘤细胞胞浆内。47例食管鳞癌组织Survivin阳性表达率为93．6％。在正常食管黏膜无阳性表达。Survivin表达水平与组织学分化程度有相关关系，高分化鳞癌中低表达者居多，而中分化鳞癌中高表达者居多，二者呈负相关（P〈0．05）。总体生存率单因素分析显示Survivin高表达组生存预后明显差于低表达组，有显著性意义（P〈0．05）。Logistic多因素回归分析显示Survivin表达水平为独立预后因素（P〈0．05）。Survivin表达水平与食管癌治疗失败（手术后3年内复发和转移死亡）有明显相关关系，高表达组发生治疗失败的病例明显增多（P〈0．01）。结论：Survivin表达水平与组织学分化程度有相关关系，为食管癌的独立预后因素；Survivin高表达预示食管癌治疗失败的机会增大。