Effects of cyclooxygenase-2 on human esophageal squamous cell carcinoma

AIM:To study the relationship between the cyclooxy-genase(COX)-2 gene and the proliferation and apopto-sis of esophageal squamous carcinoma EC109 cells.METHODS:The techniques of RNA interference(RNAi)and cell transfection,as well as the levels of oncogenic-ity in nude mice,were used to study the role of COX-2 in the esophageal squamous carcinoma cell(ESCC)line EC109.Following RNAi and transfection,Western blot-ting analysis was used to determine the expression of the COX-2 protein.The 3-(4,5-dimethylthiazol...     

Clinicopathologic significance of expression of cyclooxygenase-2 in human esophageal squamous cell carcinoma

BACKGROUND/AIMS: The focus of studies on cyclooxygenase-2 (COX2) have been on its ability to mediate the biological behavior of human tumors including tumorigenesis, tumor progression, apoptosis and differentiation. The aim of the current study was to elucidate a further finding on the clinicopathologic significance of immunohistochemical expression of COX2 in esophageal squamous cell carcinoma. METHODOLOGY: The immunohistochemical expression of COX2 was examined for 68 specimens of esophageal squamous cell carcinoma (ESCC) and the correlation of COX2 expression with clinicopathologic features was examined. COX2 immunoreactivity was weak in 27 (40%) and strong in 41 (60%) of the carcinomas. RESULTS: The proportion of poorly differentiated SCCs among tumors with a strong expression of COX2 (34%, 14 of 41) was significantly higher than among tumors with a weak expression of COX2 (19%, 3 of 14, p = 0.02). The depth of the tumors (p = 0.0004), lymph node metastasis (p = 0.009) and the stage of the tumors (p = 0.001) were advanced significantly more progressively in ESCCs with a strong COX2 expression. Moreover, survival was significantly reduced (p = 0.02) among patients with strong COX2 expression when compared with the COX2 weak group. CONCLUSIONS: This study showed that strong expression of COX2 was correlated with tumor progression and poor differentiation in ESCC.     

抑癌基因PTEN在人食管鳞癌中的表达及其意义

目的 研究食管鳞癌中PTEN的表达，探讨其与临床病理参数的关系及对患者预后的判断价值。方法 应用免疫组织化学S-P法检测62例食管鳞癌组织标本中PTEN的表达水平。结果 （1）PTEN的表达与食管壁浸润程度、淋巴结转移情况、远处转移情况、pTNM分期、肿瘤分化程度呈负相关关系（P〈0．05）。（2）高表达组患者的术后3年生存率明显低于低表达组，组间比较有统计学意义（P〈0．01）。结论 PTEN表达与反映食管鳞癌恶性度的临床病理参数呈负相关关系，是独立的预后评价因素之一。     

COX-2和MMP-9在食管鳞癌组织中的表达及其与血管生成的关系

目的: 观察食管鳞癌组织、癌旁正常黏膜中环氧化酶-2(COX-2)及基质金属蛋白酶-9(MMP-9)的表达及其与微血管密度(MVD)的关系, 探讨COX-2和MMP-9对食管鳞癌血管生成的作用与意义.方法: 应用SP法对90例食管鳞癌组织和34例癌旁正常黏膜的COX-2、MMP-9及CD34进行免疫组织化学染色, 检测癌组织、癌旁正常食管黏膜组织的COX-2与MMP-9表达及MVD, 并分析COX-2、MMP-9的表达与MVD之间, 以及他们与食管鳞癌临床病理特征之间的关系.结果: 食管鳞癌组织中COX-2、MMP-9的阳性表达率和MVD分别为84.8%、82.2%和29.70±3.82, 显著高于癌旁正常黏膜的20.6%、14.7%和15.1±2.38. COX-2的表达与肿瘤的TNM分期、分化程度和淋巴结转移密切相关( P<0.01). MMP-9、MVD的表达与肿瘤的TNM分期和淋巴结转移密切相关( P<0.01);COX-2表达与MVD呈显著正相关( r = 0.607,P<0.01); COX-2与MMP-9的表达正相关( r =0.740, P<0.01); MMP-9的表达与MVD值之间呈正相关( r = 0.718, P<0.01).结论: COX-2与MMP-9异常表达在食管鳞癌的血管生成中起重要作用, COX-2、MMP-9及其诱导的血管生成与食管鳞癌的侵袭和转移密切相关.     

Expression and clinical significance of CtBP2 in human esophageal squamous cell carcinoma

<正>Objective To explore the expression of C-terminal binding protein 2(Ct BP2)in human esophageal carcinoma and its relationship with clinicopathological parameters and survival.Methods The expression levels of CtBP2 in eight cases of fresh frozen specimens of esophageal squamous cell carcinoma(ESCC)and the adjacent e-     

COX-2在食管癌中的表达及其意义

目的通过研究COX-2和PGE2在食管癌中的表达,探讨COX-2与食管癌的关系.方法分别采用RT-PCR、免疫组织化学和放射免疫分析等方法研究食管腺癌和食管鳞癌病人内窥镜活检组织中COX-2及其mRNA的表达率以及PGE2在组织中的含量.结果RT-PCR法研究显示,食管腺癌组(88.24%)、食管鳞癌组(72.73%)中COX-2 mRNA表达率与正常组织(25.00%)相比有显著差异(P＜0.01);免疫组织化学研究显示,食管腺癌和食管鳞癌的癌细胞胞浆中COX-2蛋白呈阳性表达,食管腺癌组(76.47%)、食管鳞癌组(72.73%)中COX-2蛋白表达率与正常组织(20.00%)比有显著差异(P＜0.01).放射免疫分析法研究显示,食管腺癌组(559.22±37.77)、食管鳞癌组(563.52±41.12)中PGE2的含量(pg/mg)与对照组(357.10±37.58)相比有显著差异(P＜0.05),前两组中PGE2的含量之间无显著差异(P＞0.05).结论食管腺癌和食管鳞癌中COX-2蛋白及其mRNA均呈高表达,PGE2的含量增高.     

Expression of cyclooxygenase-2 protein in colorectal carcinomas

Summary Background. Overexpression of cyclooxygenase-2 (COX-2) has been demonstrated in various human cancers, including colorectal cancer. Thus, overexpression of COX-2 may be involved in the growth and progression of cancer, and this may have prognostic significance. Aim. The aim of our study is to evaluate the expression of COX-2 in colorectal cancer tissue, and to examine the relationship of its expression to various clinicopathological parameters and patient survival. Methods. Formalin-fixed, paraffin-embedded tissue blocks were obtained from 60 patients who underwent surgery for colorectal carcinoma in 1995 at the Chonnam National University Hospital in Gwangju, Korea. We have used an immunohistochemical technique to localize COX-2 in colorectal carcinoma tissues. Results. Immunohistochemical staining of the colorectal cancer specimens demonstrated that COX-2 expression was localized to the carcinoma cells and was not detectable in the stromal compartment of the cancers. The COX-2 immunostaining pattern was predominantly homogenous, and perinuclear cytoplasmic within the tumors. Normal colonic epithelium adjacent to the tumor showed no staining for COX-2. The COX-2 protein was detected in 70% (42/60) of colorectal carcinoma tissues. However, no significant correlation was found between COX-2 expression and various clinicopathological parameters, including histologic grade, tumor size, depth of invasion, lymph node metastasis, distant metastasis, or stage. Furthermore, COX-2 expression did not correlate with patient survival (p=0.401). Conclusion. These results suggest that COX-2 expression may play an important role in the evolution of colon carcinogenesis. However, further studies are needed to determine the prognostic relevance of COX-2.     

明胶酶B mRNA在食管癌组织中的表达

目的探讨明胶酶B mRNA在食管癌组织中表达的临床意义.方法用原位杂交法检测41例食管癌患者的癌组织及癌旁组织明胶酶B mRNA的表达.结果食管癌患者的癌组织明胶酶B mRNA的表达率(33/41)与癌旁组织的表达率(24/41)相比有显著差异(P＜0.05).有淋巴结转移食管癌患者的癌组织明胶酶B mRNA的表达率(18/19)与无淋巴结转移的表达率(15/22)相比有显著差异(P＜0.05).侵及浆膜层癌组织表达率(16/18)高于未侵及浆膜层者(17/23),但无统计学意义.结论明胶酶B在食管癌的侵袭和转移过程中可能具有重要作用.     

Nonsurgical treatments for submucosal esophageal squamous cell carcinomas

Esophageal cancer is a disease with a poor prognosis. As with superficial esophageal cancers, lymph node metastases are seen rarely if the tumors are limited to the epithelium or lamina propria, but when cancers invade the submucosa, there is a high incidence of lymph node involvement. Surgery with radical lymph node dissection is a standard treatment for treating submucosal esophageal cancers. However, it is usually associated with a reduced level of quality of life for the patients, who are often elderly and have various medical complications making them unfit for aggressive surgery. According to these background indications, various nonsurgical treatments have been developed to preserve the esophagus and to achieve a less invasive cure for such patients. Definitive radiotherapy could be a treatment option for patients with superficial carcinomas, particularly for those with mucosal cancers with an unresectable width by endoscopic mucosal resection (EMR). Although there have been some retrospective analyses with a small number of patients, they could not draw definitive conclusions. Definitive chemoradiotherapy has become one of the treatment options for patients who desire nonsurgical treatment. It has shown similar survival rates with those seen for radical surgery in two retrospective analyses and one multicenter prospective phase II study. The combination of primary EMR and prophylactic chemoradiotherapy has also shown promising results with less invasiveness than surgery. These nonsurgical approaches are now under evaluation in two multi-institutional studies run by the Japan Clinical Oncology Group (JCOG), which will clarify the optimal treatment for this disease. Review articles on this topic also appeared in the previous issue (Volume 4 Number 3). An editorial related to this article is available at .     

Flow-cytometric DNA content analysis of esophageal squamous cell carcinomas

To better understand the mechanisms of esophageal carcinogenesis, abnormalities in DNA content of esophageal squamous cell carcinomas were studied. Cellular DNA content was determined by flow cytometric study of 70 endoscopic biopsy specimens obtained from 26 patients with esophageal squamous carcinoma. High-quality histograms were obtained for 23 patients. Twenty-one patients had at least one aneuploid population in their tumor. In 7 patients, multiple aneuploid peaks were detected. Specimens from 2 patients were diploid. The interpretation of the DNA histograms was difficult in 3 patients; an aneuploid population of cells was probable in 2 of them. A statistically significant relationship was found between the degree of differentiation and DNA content abnormalities in the regions of the tumors that could be evaluated by endoscopic biopsies: well-differentiated carcinomas had diploid or small aneuploid populations containing less than 15% of the cells, whereas DNA histograms of moderately or poorly differentiated carcinomas were characterized by large aneuploid peaks representing 25%-90% of the cells and a higher proliferative fraction. No relationship was found between the size or the stage of the tumor and the DNA content detected in endoscopic biopsy samples. The frequency and the multiplicity of abnormal clones in esophageal squamous carcinomas indicates that this cancer, like esophageal adenocarcinoma, develops an association with an acquired genomic instability that produces abnormal clones of cells, according to the multistep model of neoplastic progression.     

Clinicopathological significance of vascular endothelial growth factor-C and cyclooxygenase-2 in esophageal squamous cell carcinoma

BACKGROUND: Vascular endothelial growth factor-C (VEGF-C) is a specific growth factor of lymphatics, which is known to play some role in tumor growth and metastasis to lymph nodes and distant organs in various malignancies. The purpose of the present study was to investigate the expression of VEGF-C in human esophageal squamous cell carcinomas (ESCC) to elucidate its role in tumor progression and lymph node metastasis. Another aim of the study was to investigate the relation between VEGF-C and cyclooxygenase-2 (COX-2) in ESCC. METHODS: The expression of VEGF-C and COX-2 in ESCC was evaluated in 13 endoscopic mucosal resection specimens and in 21 surgical specimens by immunohistochemical staining. Clinical data were obtained from medical records. RESULTS: The degree of VEGF-C expression increased as the depth of primary tumor progressed (r = 0.521, P = 0.002), the stage progressed (r = 0.572, P < 0.001), and the degree of COX-2 expression increased (r = 0.387, P = 0.024). The VEGF-C positive rate was different between early cancers in which regional lymph node metastasis was thought to be absent and advanced cancers in which regional lymph node metastases were confirmed after surgery (20.0% vs 100.0%; P < 0.001). CONCLUSIONS: The VEGF-C expression in ESCC is related to COX-2 expression, and VEGF-C is also associated with the depth of primary tumor, the stage, and probably lymph node metastasis. Thus the investigation of VEGF-C expression in ESCC may assist in management planning.     

Telomeric associations of chromosomes in patients with esophageal squamous cell carcinomas

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AnxA1在食管鳞状细胞癌组织中的表达及意义

目的研究膜联蛋白A1(AnxA1)在食管鳞癌组织中的表达及其在食管鳞癌发生发展中的作用。方法应用免疫组化SABC法检测48例食管鳞癌、35例癌前病变(21例低级别上皮内瘤变、14例高级别上皮内瘤变)和18例正常对照组织中AnxA1的表达,并结合其临床病理资料进行分析。结果 AnxA1的阳性表达率在正常食管鳞状上皮组织、低级别上皮内瘤变组织、高级别上皮内瘤变组织及食管鳞状细胞癌组织中的表达分别为100%(18/18)、57.1%(12/21)、7.1%(1/14)和6.3%(3/48)。正常食管鳞状上皮组织AnxA1阳性表达率与其他三组AnxA1阳性表达率的差异有统计学意义(P0.05)。结论从食管正常组织到癌前病变组织以至鳞状细胞癌组织中,AnxA1的表达逐渐降低,提示其与食管鳞癌的早期癌变相关。     

食管鳞癌中Dickkopf-3蛋白的表达

目的 探讨Dickkopf-3(Dkk-3)在不同分化程度的食管鳞癌、正常食管黏膜组织中的表达及其与食管鳞癌生物学行为的关系.方法 采用免疫组化S-P法,检测Dkk-3蛋白在67例食管鳞癌组织及5例非瘤食管组织的组织芯片中的表达情况,并结合临床病理资料进行分析.结果 67例食管鳞癌组织中Dkk-3蛋白阳性率为65.7%(44/67),5例非瘤食管组织中只有1例的微血管中Dkk-3蛋白表达阳性.Dkk-3蛋白的阳性表达与食管鳞癌纤维膜浸润、淋巴结转移、浸润深度和TNM分期呈正相关(P<0.05),而与性别、年龄、病理分级的相关性均无统计学意义(P>0.05).结论 Dkk-3在食管鳞癌中高表达,其可能参与了食管鳞癌的浸润及转移,有助于对食管鳞癌发展的判断和预测有无淋巴结转移.     

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。     

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。