Expression analysis of BRUCE protein in esophageal squamous cell carcinoma

Apoptosis is a form of cell death in response to diverse stressful physiological or pathological stimuli. One of the most important gene families involved in apoptosis is inhibitors of apoptosis. As a member of inhibitors of apoptosis, BRUCE can suppress apoptosis and promote cell division. Because esophageal squamous cell carcinoma (ESCC) cells, as well as other cancer cells, are immortal, our aim in this study was to analyze BRUCE protein expression in ESCC and evaluate its correlation with tumoral clinicopathologic features. Fifty ESCC specimens were examined for BRUCE protein expression using immunohistochemistry. A defined scoring method was applied. BRUCE protein was detected in 82% of tumors. Tumor progression stage and invasion depth correlated significantly with BRUCE protein expression (P = .019 and .005, respectively). Furthermore, association of BRUCE expression with tumor location was near significant (P = .058). The correlation of BRUCE overexpression in ESCC and disease aggressiveness may confirm the importance of BRUCE in ESCC progression and invasiveness. Therefore, BRUCE protein may be a molecular marker for aggressive ESCC and, thus, a potential therapeutic target to inhibit tumor cell progression and invasion.     

Expression of Akt and Mdm2 in human esophageal squamous cell carcinoma

The Akt-Mdm2 pathway plays an important role in carcinogenesis in a variety of malignant tumors. However, the Akt-Mdm2 pathway in esophageal squamous cell carcinoma (ESCC) has not been fully studied. We investigated the proteins and mRNA expression of Akt and Mdm2 to elucidate the roles of these proteins in ESCC. We also examined the effect of Akt knockdown on Mdm2 expression in ESCC cells. ESCC tissue samples were obtained from 23 individuals who underwent surgical resection with no preoperative treatment. Akt1-3 and Mdm2 gene and protein expression were analyzed. The effect of siRNA-mediated Akt knockdown on Mdm2 expression was also studied, using ESCC cell lines. Akt1 and Mdm2 immunoreactivity was detected in 77.8 and 66.7% of tumor specimen from ESCC patients, respectively. Akt1 and Mdm2 mRNA expressions were correlated and significantly elevated in tumor tissue (p < 0.0001 and p < 0.05, respectively). The siRNA-targeted reduction of each Akt isoform reduced Mdm2 protein expression. The overexpression of Akt1 and Mdm2 may be related to esophageal carcinogenesis. Furthermore, Akt expression regulates Mdm2 expression, which may in turn regulate the function of wild-type p53. These results may provide the basis for future preventative or clinical therapies for esophageal cancer.     

Expression of Bax and apoptosis-related proteins in human esophageal squamous cell carcinoma including dysplasia.

The rate of tumor growth depends on the balance between proliferation and death of tumor cells. It is known that Bax, caspase-3, and p53 proteins are death-promoting factors, whereas Bcl-2 protein is a death antagonist. We immunohistochemically examined the expression of Bax and apoptosis-related proteins such as caspase-3, p53, and Bcl-2 in 76 patients with human esophageal squamous cell carcinoma (SCC) including dysplasia to determine the relationship of expression of each protein to tumor behavior and patients' prognosis. No significant relationships in immunopositivity were found among these proteins in SCCs. Cytoplasmic Bax expression was exhibited in 63 cases of SCCs (82.9%). The apoptotic index of caspase-3-positive lesions was significantly higher than that of caspase-3-negative lesions in both dysplasia and SCC (P =.016, P =.012). On the other hand, the apoptotic index (1.18%) was significantly correlated with Bax overexpression in dysplasia (P =.006), but not in SCC lesions (P =.129). The patients with Bax-positive SCCs were found to have a poor prognosis by the Kaplan-Meier method (P =.043). These findings suggested that Bax expressed in dysplasia may play a role as an apoptotic factor, but that it may be functionally inactive in some cancerous lesions and thus not contribute to suppression of the tumor progression in some cases of human esophageal SCCs.     

Expression profiling of micro-RNAs in human esophageal squamous cell carcinoma using RT-PCR

To develop novel therapeutic and diagnostic methods for esophageal cancer, it is important to understand the precise biological mechanism. Micro-RNAs (miRNAs) seem to be crucial factors in diverse regulation pathways. In this study, we analyzed the expression of mature miRNAs in esophageal squamous cell carcinoma (ESCC). The expression of 73 miRNAs was quantified by qRT-PCR in 30 primary ESCC specimens. We examined the correlation between miRNA expressions and the clinicopathological factors and prognosis of ESCC. The Kaplan-Meier survival curves showed that the high expression levels of 6 of the 72 miRNAs correlated with significantly lower patient survival rates. The overexpression of miR-129 was identified as a significant and independent prognostic factor (P = 0.031) in surgically treated ESCC patients. The hazard ratio for the prediction of early death was 18.11 for high versus low expression levels of miR-129. Similar results were obtained from an analysis performed on an additional 19 patients (test cohort) (P = 0.0057, for training cohort; P = 0.011, for test cohort; log-rank test). This experiment supports the notion that the high miR-129 expression levels, as observed in this study, might play a important role in the development of esophageal cancer.     

骨桥蛋白在食管鳞癌中的表达及其临床意义

目的观察骨桥蛋白（OPN）在食管鳞癌组织、癌旁组织和转移淋巴结的表达状况,探讨OPN在食管鳞癌中表达的临床意义。方法运用免疫组化S-P法检测44例食管鳞癌组织、癌旁组织和20例转移淋巴结免疫组化染色。结果OPN在食管癌组织、癌旁组织及转移淋巴结中的表达率分别为86．3％、0％和100％。癌组织中OPN主要表达于肿瘤细胞的细胞浆中。OPN的表达与肿瘤TNM分期、淋巴结转移状态有关,而与肿瘤位置、肿瘤直径、浸润深度及病理学分级无关。OPN在癌组织、癌旁组织及转移淋巴结表达强度亦存在显著性差异。结论食管鳞癌组织中OPN主要由肿瘤细胞产生。OPN与肿瘤的浸润、转移有关,反映了肿瘤的生物学特性。     

NOB1mRNA在人食管鳞癌组织的表达及其临床意义

目的 探讨NOB1 mRNA(nin one binding protein)在食管鳞癌(esophageal squamous cell carcinoma,ESCC)患者组织中的表达及其与临床病理参数之间的关系.方法 运用RT-PCR方法检测19例ESCC患者癌组织及对应的癌旁组织中NOB1 mRNA的表达情况,分...     

食管鳞状细胞癌中MCM2蛋白与Ki-67的表达及对比研究

目的 探讨微小染色体维持蛋白2(minichromosome maintenance 2 protein,MCM2)与Ki-67在食管癌中的表达及两者表达的差异和相关性.方法 采用免疫组化EliVision方法,分别检测90例食管鳞状细胞癌组织中MCM2,Ki-67的表达,计算其标记指数(labeling index,LI),分析MCM2,Ki-67在食管鳞癌中的表达及两者之间的差异和相关性.结果 90例食管癌组织均表达MCM2及Ki-67抗原,其中MCM2 LI高于Ki-67,两者差异有统计学意义(P＜0.05).同时显示MCM2及Ki-67的表达与食管鳞癌的分化程度具有相关性,MCM2在食管鳞癌各级组织间表达差异均有统计学意义(P＜0.01),而Ki-67只在Ⅰ级与Ⅲ级食管鳞癌组织间差异有统计学意义(P＜0.01).并且MCM2与Ki-67在食管鳞癌中的表达呈正相关关系(P＜0.01).结论 MCM2是优于Ki-67的细胞增殖标记物,可用于对食管鳞癌的分级和判断食管鳞癌恶性程度的高低.     

人食管鳞癌组织中RhoC和Ki-67的表达及意义

 目的：检测人食管鳞癌组织中RhoC和Ki-67的表达,探讨它们在食管鳞癌发生发展中的作用及相关性。方法：采用免疫组织化学方法（二步法）,检测分析52例人食管鳞癌组织中RhoC和Ki-67蛋白的表达情况及其与患者临床病理特征的关系。结果：（1）食管鳞癌组织RhoC蛋白的阳性表达率为61.5%（32/52）,相应癌旁组织RhoC阳性表达率为29.7%（11/37）,差异显著（P＜0.05）。（2）RhoC表达与食管鳞癌临床TNM分期和淋巴结转移密切相关,TNM Ⅲ期食管鳞癌组织中RhoC阳性表达率为78.3%（18/23）,显著高于TNM Ⅰ～Ⅱ期的48.3%（14/29）（P＜0.05）;伴有淋巴结转移的食管鳞癌组织中RhoC阳性表达率为81.8%（18/22）,显著高于无淋巴结转移的46.7%（14/30）（P＜0.05）。（3）食管鳞癌组织中,RhoC与Ki-67的表达呈显著正相关（r=0.322,P＜0.05）,均呈升高趋势。结论：RhoC的高表达与食管鳞癌的分期、淋巴结转移及细胞增殖密切相关。RhoC可成为食管鳞癌早期诊断和判断预后的辅助指标。     

Expression and prognostic value of FOXP1 in esophageal squamous cell carcinoma

BackgroundForkhead box protein P1 (FOXP1) has been suggested as a prognostic marker in several malignant tumors. However, the significance of FOXP1 in esophageal squamous cell carcinoma (ESCC) is still unclear. The purpose of this study was to investigate the expression pattern of FOXP1 in normal esophageal tissue and ESCC and to analyze the clinicopathological significance and prognostic value of FOXP1 in ESCC.MethodsFOXP1 was detected by immunohistochemistry using tissue microarrays containing tumor tissues and adjacent normal tissues from 270 ESCC patients with oncological follow-up data.ResultsNormal esophageal tissues predominantly showed an exclusive nuclear FOXP1 (n-FOXP1) expression pattern, and no exclusive cytoplasmic FOXP1 (c-FOXP1) staining was found. In ESCC, the expression rates of exclusive n-FOXP1-positive, exclusive c-FOXP1-positive, both nuclear and cytoplasmic positive and complete negative were 14.4%, 28.9%, 10.4% and 46.3%, respectively. High n-FOXP1 expression was significantly correlated with decreased postoperative recurrence and distant metastasis (P < 0.05). Furthermore, elevated c-FOXP1 expression was significantly associated with regional lymph node metastasis and distant metastasis (P < 0.05). High c-FOXP1 expression had an effect on shorter overall survival (OS) time, but the difference was not statistically significant (P > 0.05). Kaplan–Meier analysis showed that ESCC patients with high n-FOXP1 expression survived significantly longer than patients with low n-FOXP1 expression. Multivariate analysis confirmed that patients with high n-FOXP1 staining exhibit good prognosis and n-FOXP1 was an independent factor for ESCC prognosis.ConclusionsOur results suggest that FOXP1 plays an essential role in ESCC progression and prognosis and may be a useful biomarker for predicting survival.     

食管鳞癌HPV感染与病毒致癌基因E6的关系

目的：探讨人乳头瘤病毒（ＨＰＶ）与食管鳞状细胞癌的关系。方法：采用多重引物多聚酶链反应（ＰＣＲ）的免疫组化技术、对１０４例食管鳞癌进行ＨＰＶ ＤＮＡ和病毒癌基因Ｅ６蛋白检测。结果：ＨＰＶ ＤＮＡ阳性者占５０．９６％（５３／１０４），其中ＨＰＶ１６型ＤＮＡ４９．０６％（２６／５３），ＨＰＶ１８型 ＤＮＡ５．６％（３／５３），ＨＰＶ６／１１ ＤＮＡ７．５％（４／５３）；两上或三个类型的混合感染占３７．     

Nrf2在食管鳞癌组织中的表达及意义

目的:探讨Nrf2(Nuclear factor E2 p45-related factor2)在食管鳞癌组织中的表达及其与临床病理学特征的关系。方法:采用免疫组化SP法检测Nrf2在32例食管鳞癌,30例癌旁组织,21个阳性淋巴结和24个阴性淋巴结组织中的表达。结果:Nrf2阳性表达主要定位于细胞核中,在食管鳞癌中的阳性表达率为78.13%,显著高于癌旁组织(13.33%),淋巴结癌转移阳性组织中的表达率(66.67%)也显著高于淋巴结癌转移阴性组织中的表达水平(20.83%),均具有统计学意义(P<0.05)。Nrf2的阳性表达随淋巴结的转移度的增加而表达增加(P<0.05),但在不同年龄、性别、TNM分期、肿瘤分化程度及不同部位之间差异无统计学意义。结论:Nrf2在食管鳞癌中高表达,表达的高低与淋巴结转移与否及转移度有关。     

Ubiquitous p63 expression in human esophageal squamous cell carcinoma

p63, a recently identified member of the p53 gene family, plays an important role in human tissue functions. We examined the pattern of p63 expression in human esophageal squamous cell carcinomas including early-stage cancers, and its clinicopathological significance. Immunoreactivity for p63 was detected in 96.9% (63/65) esophageal squamous cell carcinomas. Diffuse p63 expression was seen in 75.4% (49/65). p63 was detected not only in the in situ carcinomatous components or intramucosal carcinomas, but also in the invasive carcinomatous parts of the p63-positive cases. There were no significant correlations between p63 expression and clinicopathological features, such as depth of tumor invasion, tumor differentiation, lymph node metastasis and venous/lymphatic invasion. We also analyzed the relationship between p63 and p53 expression in esophageal squamous cell carcinomas. These results suggest that the p63 gene, as well as the p53 gene, play a major role in the carcinogenesis of human esophageal squamous cells and in the growth of the carcinoma.     

Expression of cyclooxygenase-1 and cyclooxygenase-2 in human esophageal mucosa, dysplasia and carcinoma.

OBJECTIVE: COX (cyclooxygenase), a prostaglandin H synthase, catalyzes the rate-limiting step in prostaglandin biosynthesis. Two isoforms of COX have been identified: COX-1 and COX-2. We examined the expression of COX-1 and COX-2 in esophageal normal mucosa, dysplasia and squamous cell carcinoma (SCC). METHODS: The expression of COX-1 and COX-2 in 80 surgically removed esophagi due to SCC, as well as in 5 human esophageal SCC cell lines was analyzed, using immunohistochemistry and Western blot analyses. RESULTS: COX-1 and COX-2 were variably expressed in the SCC cell lines. Higher COX-1 expression was noted in 31 (41.9%) of the 74 specimens of normal mucosa, in none of the 40 specimens of dysplastic mucosa and in 15 (18.8%) of the 80 specimens of SCC, the frequency being significantly higher in normal mucosa than in dysplasia or SCC (p < 0.0001, p = 0.0018, respectively). COX-1 expression was significantly higher in well-differentiated SCC than in moderately or poorly differentiated SCC (p < 0.01). Higher COX-2 expression was noted in none (0.0%) of the specimens of normal mucosa, in 12 (30%) of the specimens of dysplastic mucosa, and in 41 (51.3%) of the speciments of SCC, the frequency being significantly higher in SCC than in normal mucosa or dysplasia (p < 0.0001, p = 0.0278, respectively). CONCLUSIONS: COX-1 is expressed in normal esophageal mucosa and is occasionally induced in well-differentiated SCC, whereas COX-2 expression is more characteristic of dysplasia and carcinoma than of normal mucosa, implying a possible association with cell differentiation in the former, and esophageal tumorigenesis in the latter.     

食管鳞状细胞癌中血管内皮生长因子C mRNA的表达及其临床意义

目的:探讨食管鳞状细胞癌中血管内皮生长因子C(VEGF-C)的表达及临床意义。方法:收集中山大学附属第一医院2009年3月~2010年2月收治的39例食管鳞状细胞癌患者,采用原位杂交法检测肿瘤组织及正常食管组织中VEGF-CmRNA的表达情况,并进行随访观察。结果:食管鳞状细胞癌组织中VEGF-CmRNA表达阳性率为71.8%(28/39),正常食管组织中表达阳性率为12.8%(5/39),两者比较差异有统计学意义(P<0.05)。VEGF-CmRNA的表达与食管鳞状细胞癌的淋巴结转移和浸润深度有关,但与性别、年龄和肿瘤组织分化程度无关。随访至死亡或2012年2月29日(以先者为准),VEGF-CmRNA阳性组生存率低于阴性组,差异有统计学意义(P<0.05)。结论:VEGF-CmRNA的表达与食管鳞状细胞癌的发展、淋巴结转移及预后有相关性。     

Expression of HLA-G is associated with prognosis in esophageal squamous cell carcinoma

The detection of HLA-G expression might serve as a clinical marker in the diagnosis or prediction of clinical outcomes for certain types of carcinoma. The aim of this study was to determine whether the detection of HLA-G has any important clinical applications for patients with esophageal squamous cell carcinoma (ESCC) by using immunohistochemical methods. We observed that the HLA-G protein was expressed in 90.9% (110/121) of the primary sites of ESCC but not in the normal esophageal tissues. The expression of HLA-G in the tumors was significantly correlated with histologic grade, depth of invasion, nodal status, host immune response, and clinical stage of disease. Patients with positive HLA-G expression had a significantly worse prognosis. In multivariate analysis, HLA-G was an independent prognostic factor. Our results indicate that expression of HLA-G is a characteristic feature of ESCC and suggest that immunostaining by anti-HLA-G antibodies may be a potentially useful prognostic indicator.     

Expression and clinical significance of B cell translocation gene 2 in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is widely known as a highly fatal cancer, and thus it is important to identify tumor-specific and radiosensitivity-specific markers in ESCC. B cell translocation gene 2 (BTG2) has been considered a novel tumor suppressor gene or radiotherapy sensitivity-associated gene. However, the relationship between BTG2 and ESCC development and radiotherapy sensitivity is uncertain. The present study aims to explore the expression and clinical significance of B cell translocation gene 2 (BTG2) in ESCC by analyzing the RNAseq data from the TCGA and immunohistochemical staining of ESCC samples. We found that the level of BTG2 mRNA was significantly decreased in ESCC patients, and further decreased significantly in radiotherapy resistant patients compared to sensitive patients. The positive expression rate of BTG2 protein was 56.0% (103/184) in 184 ESCC tissue samples and 84.0% (42/50) in normal esophageal mucosal samples, respectively. The positive ratios of BTG2 expression in radiotherapy-sensitive group and radiotherapy resistant group were 57.9% (22/38) and 23.5% (4/17), respectively. Furthermore, the analysis indicates that the expression level of BTG2 significantly correlated with lymph node metastasis and clinical staging in ESCC patients. A multivariate analysis with Cox regression model showed that BTG2 level was an independent risk factor affecting the prognosis of ESCC patients. Above all, the downregulation of BTG2 may be used as a molecular marker to identify and predict ESCC progression and radiosensitivity.     

Altered expression and localization of desmoglein 3 in esophageal squamous cell carcinoma

Desmoglein 3 (DSG3), a transmembrane cadherin of the desmosomal cell–cell adhesion structure, plays vital roles in the maintenance of normal epithelial tissue architecture. Reports implicating a role for DSG3 expression in cancer are few and contradictory. In this study, immunohistochemical staining was employed to investigate DSG3 expression and subcellular localization in esophageal squamous cell carcinoma (ESCC), and to correlate changes with clinical characteristics. Results indicate that in normal squamous cell epithelia, strong DSG3 immunoreactivity was observed in the Stratum spinosum, and localization occurred only at the cell membrane. In ESCC, DSG3 immunoreactivity displayed an abnormal cytoplasmic localization that was correlated with cell differentiation (P = 0.018). Most strikingly, in 74.1% of the tumors, DSG3 expression was up-regulated and correlated with regional lymph node metastasis (P = 0.036). Moreover, in patients without lymph node metastasis, cytoplasmic localization of DSG3 correlated with poor prognosis (P = 0.044). These results suggest that DSG3 is involved in the development of ESCC and imply that DSG3 overexpression is likely to be an essential contributor to the aggressive features of esophageal cancer.     

肺鳞状细胞癌中死亡相关蛋白激酶的表达

目的　检测肺鳞状细胞癌中死亡相关蛋白激酶 (DAP K)mRNA表达及细胞凋亡 ,探讨DAP K与细胞凋亡的关系及其在肺鳞状细胞癌发生、发展中的作用。方法　用原位分子杂交法检测 6 0例肺鳞状细胞癌、9例癌旁肺组织DAP KmRNA表达 ;用原位末端标记TUNEL法检测相应组织中细胞凋亡 ,计算凋亡指数 (AI)。结果　肺鳞状细胞癌的DAP KmRNA阳性表达率为 4 6 7% ,癌旁肺组织为 6 7 7% ,其阳性率高于肿瘤组织 (P <0 0 1 )。在肺鳞状细胞癌中 ,高分化癌DAP KmRNA阳性率为 70 % ,低分化癌为 2 3 3% ,高分化癌的DAP KmRNA阳性率高于低分化癌 (P <0 0 1 )。肺鳞状细胞癌的细胞AI为(0 6 72 8± 0 4 2 6 1 ) % ,癌旁肺组织中支气管肺泡上皮细胞AI为 (1 0 2 89± 0 2 4 33) % ,癌旁肺组织的AI高于肿瘤组织 (P<0 0 1 )。在肺鳞状细胞癌中 ,高分化癌的AI为 (0 5 82 3± 0 1 92 2 ) % ,低分化癌为 (0 4 4 6 0± 0 1 92 5 ) % ,高分化癌的AI高于低分化癌 (P <0 0 1 )。DAP KmRNA呈阳性表达的肺癌 ,其AI为 (0 5 31 7± 0 2 0 97) % ;DAP KmRNA呈阴性者 ,其AI为 (0 4 872± 0 1 91 8) % ,两组间差异有显著性 (P <0 0 5 )。在连续切片上 ,DAP KmRNA阳性细胞的分布区域与凋亡阳性细胞的分布相似。DAP KmRNA呈阳性表达