Increased expression of DLX2 correlates with advanced stage of gastric adenocarcinoma

AIM:To investigate the expression of distal-less homeobox 2 (DLX2) in gastric adenocarcinoma and its clinicopathological significance. METHODS:Gastric adenocarcinoma tissues were obtained from gastrectomy specimens of 129 patients from the Department of Surgery and Pathology, the Second Affiliated Hospital of Kunming Medical University. Sixty cases of normal gastric tissues were collected from gastrectomy specimens of adjacent gastric cancer margins greater than 5 cm. Patient diagnosis was established pathologically, and no patient had received chemotherapy or radiotherapy before surgery. All tissue specimens were formalin-fixed and paraffin-embedded. Immunohistochemistry was carried out to investigate the expression of DLX2 in 129 gastric adenocarcinoma tissues and 60 adjacent normal tissues. The immunos-taining reaction was semiquantitatively evaluated based on the proportion of positive cells and the median staining intensity in normal gastric epithelial cells or tumor cells. All patients had follow-up records for more than 5 years. Correlations of DLX2 expression with clinicopathological features and prognosis of patients with gastric adenocarcinoma were analyzed. All statistical analyses were performed using the SPSS 17.0 software. RESULTS:The positive expression of DLX2 was detected in 68 (52.7%) cases of 129 gastric adenocarcinoma tissues and 14 (23.3%) cases of 60 adjacent normal tissues. The difference in DLX2 expression between gastric adenocarcinoma tissues and adjacent normal tissues was statistically significant (Ⅹ2 = 14.391, P < 0.001). Moreover, high expression of DLX2 was detected in 48 (37.2%) cases of 129 human gastric cancer tissues, but not in adjacent normal tissues. The expression of DLX2 correlated with the size of tumor (P = 0.001), depth of invasion (P = 0.008), lymph node metastasis (P = 0.023) and tumor-node-metastasis stages (P = 0.020), but was not correlated with age, gender, histological differentiation and distant metastasis. The Kaplan-Meier survival analysis revealed that survival time of patients with high DLX2 expression was significantly shorter than that with low DLX2 expression. However, the multivariate analysis showed that invasion depth (P < 0.001), lymph nodes metastasis (P = 0.001) and distant metastasis (P < 0.001) were independent prognostic factors for patients with gastric adenocarcinoma, but DLX2 expression, tumor location and tumor size were not. CONCLUSION:These results suggest that increased expression of DLX2 may correlate with the advanced stage of gastric adenocarcinoma, and it may contribute to tumor development.

食管胃交界腺癌和远端胃腺癌中HER2、RKIP及ERK表达的对比研究

目的:比较HER2、RKIP和ERK在食管胃交界腺癌(adenocarcinoma of esophagogastric junction,AEG)及远端胃腺癌(distal gastric adenocarcinoma,DGA)中的表达情况,并探讨AEG与DGA发病机制的差异。方法:通过免疫组化法检测AEG、DGA及正常胃黏膜组织中HER2、RKIP及ERK的表达情况,分析HER2、RKIP及ERK与临床病理学特征的关系及三者相关性。结果:AEG中HER2阳性表达率高于DGA,差异有统计学意义(P<0.05)。AEG及DGA中RKIP阳性表达率均低于正常胃黏膜组织,ERK阳性表达率均高于正常胃黏膜组织(P<0.05)。AEG中,RKIP在高/中分化、淋巴结转移组中阳性表达率较低,ERK在低分化、浸润浆膜层、淋巴结转移组中阳性表达率较高(P<0.05);HER2与ERK表达正相关(r=0.352,P=0.007),RKIP与ERK表达负相关(r=-0.521,P=0.000)。DGA中,RKIP在低分化、淋巴结转移组中阳性表达率较低,ERK在淋巴结转移组中阳性表达率较高(P<0.05);RKIP与ERK表达负相关(r=-0.287,P=0.021)。结论:AEG中HER2阳性表达率高于DGA,ERK高表达与AEG患者临床病理特征的关系更为密切,RKIP表达与AEG和DGA的分化程度和淋巴结转移情况密切相关。HER2、RKIP、ERK在AEG与DGA中的表达不同,提示不同部位胃腺癌的MAPK信号通路调节机制并不完全一致。

An Asian population-based survival analysis of patients with distal esophageal and gastric cardia adenocarcinomas

Background Gastroesophageal junction adenocarcinomas include adenocarcinomas of the distal esophagus （DE） and gastric cardia （GC）. It is controversial whether these tumors are the same entity and whether they have the same survival rates. Patients with DE and GC adenocarcinomas have a similar survival rate in the US; however, data are lacking in Asian countries. Therefore, we conducted a retrospective study to understand the implications of the tumor location in the survival of Asian patients. Methods A total of 209 patients with pathologically confirmed DE and GC adenocarcinomas, from 2005 to 2007, were included in the study. We identified patients with adenocarcinomas of the DE （DE group, n=91） and GC （GC group） （n=118）, We performed an unadjusted survival analysis using the Kaplan-Meier method, and used a Cox proportional hazards regression model to adjust for potential confounding covariates. Results We found no significant difference between the overall survival of the DE and GC groups. The 3-year survival rates were 44.8% and 53.0%, respectively, and the 5-year survival rates were 27.9% and 30.2%, respectively （P=0.162）. We found no significant difference in early staging, advanced staging, different T staging, and different N staging, between the groups. Both advanced post-operative N staging and advanced AJCC staging had a significant adverse effect on survival. Conclusions Patients with DE and GC adenocarcinomas have similar survival rates in the Asian population. Both post-operative N staging and AJCC staging are prognostic factors.

食管胃交界腺癌和远端胃癌KLF4 SP1及Cyclin D1表达的对比研究

目的:近些年研究发现胃食管交界腺癌的发生率较远端胃癌明显升高,但其发生机制目前并不清楚,本研究通过对比观察KLF4、SP1和Cyclin D1在食管胃交界腺癌和远端胃癌表达的差异,探讨食管胃交界腺癌发生的可能机制。方法:采用免疫组织化学染色法对比观察58例食管胃交界腺癌和47例远端胃癌组织中KLF4、SP1和Cyclin D1在蛋白水平上的表达差异以及与淋巴结转移的关系。结果:KLF4在远端胃癌组中的阳性表达率明显低于食管胃交界腺癌组(P<0.05);而且远端胃癌高中分化组和低分化组中KLF4的阳性表达率均明显低于相应食管胃交界腺癌组(P<0.05)。SP1在远端胃癌组中的阳性表达率明显高于食管胃交界腺癌组(P<0.05);而且远端胃癌高中分化组中SP1的阳性表达率均明显高于相应食管胃交界腺癌组(P<0.05)。Cyclin D1在食管胃交界腺癌组和远端胃癌组中的阳性表达率未见明显差异。进一步观察KLF4、SP1和Cyclin D1与淋巴结转移的关系,结果发现Cyclin D1的高表达与食管胃交界腺癌淋巴结转移有关;而KLF4、SP1和Cyclin D1的表达异常均与远端胃癌淋巴结转移有关。相关性分析结果显示在食管胃交界腺癌中KLF4与SP1和Cyclin D1之间未见明显相关关系;而在远端胃癌中KLF4与SP1以及KLF4与Cyclin D1(r=-0.334,r=-0.341,P<0.05)之间呈负相关;SP1与Cyclin D1之间呈正相关(r=0.340,P<0.05)。结论:食管胃交界腺癌和远端胃癌组织KLF4、SP1和Cyclin D1的表达和临床病理意义均存在一定差异,提示两种肿瘤在发生发展方面可能有所不同。

miRNA-204在胃远端腺癌中的表达及作用初探

目的筛选胃远端腺癌中差异表达的miRNAs,并就其在胃癌发生、发展中的作用及机制进行初步研究。方法采用miRNA芯片,对胃远端(体、窦)腺癌组织及配对正常组织进行检测,筛选胃远端腺癌差异表达的miRNAs,并观察其与临床病理因素的关系;运用TargetScan等生物信息学方法,预测特定miRNA可能的靶基因。结果芯片检测发现共47条miRNAs在胃远端腺癌组织和配对正常组织中表达差异显著;实时荧光定量PCR验证了miR-204的表达在肿瘤组织中下调;生物信息学分析显示BCL-2、NR3C1和SOCS6等可能为miR-204的靶基因。结论胃远端腺癌有其独特的miRNA表达谱;预测BCL-2,NR3C1和SOCS6等可能为miR-204的靶基因。

食管-胃交界处腺癌的临床病理特征分析

目的分析食管-胃交界部腺癌（adenocarcinoma of the esophagogastric junction,AEG）的临床及病理特征,探讨贲门腺癌与贲门下腺癌、食管下段腺癌之间的临床病理特征差异及临床意义。方法回顾性分析2006年1~12月在四川大学华西医院行手术治疗且经病理明确诊断为胃食管交界处腺癌的204例患者的临床及病理特征。结果贲门腺癌淋巴结转移率为84.8%,食管腺癌淋巴结转移率为87.3%,贲门下腺癌淋巴结转移率为69.0%,转移率差异有统计学意义（P〈0.05）。贲门腺癌、食管腺癌、贲门下腺癌患者根治术后3年生存率分别为25.0%、42.9%、52.9%。结论 AEG预后均较差,术后预后主要受肿瘤分期以及淋巴结转移等情况影响。

食管胃交界腺癌和远端胃癌中hMLH1和hMSH2表达及其意义

目的 分析hMLH1和hMSH2在食管胃交界腺癌和远端胃癌中的表达情况,探讨其在不同部位胃癌发生发展中的可能意义.方法 采用免疫组织化学染色法,对比检测52例食管胃交界腺癌和17例远端胃癌hMLH1和hMSH2在蛋白水平上的表达情况,分析表达差异及其临床病理意义.结果 食管胃交界腺癌组织中,hMLH1和hMSH2蛋白表达率分别为55.8％（29/52）和63.5％（33/52）,远端胃癌中hMLH1和hMSH2蛋白的表达率分别为41.2％（7/17）和70.6％（12/17）,两者的阳性表达率差异无统计学意义（P＞0.05）.食管胃交界腺癌和远端胃癌hMLH1和hMSH2的表达与肿瘤的分化程度以及淋巴结转移均无明显相关性（P＞0.05）.结论 hMLH1和hMSH2并不是食管胃交界腺癌和远端胃癌发生机制差异性的关键分子.

胃食管结合部腺癌与中远端胃癌术前同步放化疗研究进展

胃癌在我国发病率高居第二位,初诊胃癌患者分期晚,单纯手术的根治性切除率低且术后复发率高,整体预后较差,同步放化疗作为局部治疗方式在胃癌中逐渐体现出重要价值。近年来,虽然中远端胃癌患者仍然是主要患病人群,但随着生活习惯的改变,胃食管结合部腺癌患者发病数量逐渐上升,其预后相对中远端胃癌差。已有大型Ⅲ期研究证实了术前同步放化疗可以提高胃食管结合部腺癌的降期率及局部控制率。但是中远端胃癌仍缺乏Ⅲ期研究证据,尚需更多临床研究来探索同步放化疗的价值。本文将分别对胃食管结合部腺癌和中远端胃癌术前同步放化疗的研究现况进行阐述。