VEGF和抑癌基因maspin在胃癌组织中的表达及意义

目的观察血管内皮生长因子（VEGF）和抑癌基因maspin在胃癌组织中的表达情况,研究它们与胃癌临床特征的关系。方法应用免疫组化法检测102例胃癌患者手术切除的癌组织和癌周正常组织中VEGF和maspin表达水平。结果VEGF在正常胃组织中未见表达,在胃癌组织中的表达率为50.0%,两者比较差异有显著性意义（P〈0.01）。maspin在正常胃组织中表达率为87.3%,在胃癌组织中的表达率为52.0%,两者比较差异有显著性意义（P〈0.01）。VEGF蛋白表达水平与胃癌浆膜浸润、TNM分期、淋巴结转移、5年生存率有关（P〈0.05）,maspin蛋白表达水平与胃癌浆膜浸润、淋巴结转移、5年生存率有关（P〈0.05）。结论同时检测胃癌组织中VEGF与maspin表达水平,对判断胃癌浸润转移潜能及评估患者预后有一定参考价值。     

Simultaneous comparison of multiple molecules using tissue array analysis in the thyroid neoplasm

Aim: Differential diagnosis, including the respective distinctions between benign and malignant tumors, follicular and papillary neoplasms, and follicular adenoma and follicular carcinoma, are always required in clinical practice, because therapeutic strategy largely depends on the diagnosis made. Methods: The present study describes a novel approach to obtaining clinically useful markers by means of the simultaneous comparison of multiple molecules using tissue array analysis. The markers examined in this study include galectin‐3, CD44v6, p53, HBME‐1, maspin and S100A4, which were reportedly useful for making these distinctions in association with metastasis and invasion. A total of 45 cases of thyroid tumors (seven adenomatous goiters, 16 follicular adenomas, 12 follicular carcinomas and 10 papillary carcinomas) were analyzed. Results: The results demonstrated the following suggestive phenotypes: galectin‐3^‐, HBME‐1^‐ and maspin⁺ as benign lesions, galection‐3^‐, HBME‐1⁺ and maspin^‐ as follicular carcinoma, and galectin‐3⁺, HBME‐1⁺ and maspin⁺ as papillary carcinoma. Conclusions: The expression of the molecules was assessed in each case and the expression profiles were compared. Useful multiple molecules were selected for each distinction and were correlated with each other. To understand the complex relationship, a logistic regression model was constructed. These results suggested that combined analysis of multiple molecules enhanced the differential diagnostic accuracy.     

转染maspin cDNA在胃癌细胞中的表达及其对uPA和uPAR表达的影响

目的 研究转染maspin cDNA在胃癌细胞中的表达及其对uPA和uPAR表达的影响,探讨maspin基因抑制胃癌浸润转移的机制.方法 构建 maspin/PCR2.1表达载体,转染胃癌细胞株MKN28和SGC7901,用RT-PCR和Western blot检测maspin基因,uPA和uPAR表达的变化.结果 经酶切证实,得到正向插入的真核表达质粒maspin/PCR2.1.成功转染到MKN28和SGC7901细胞中并表达,uPA和uPAR的mRNA和蛋白表达均降低.结论 成功构建了maspin/PCR2.1表达载体,maspin基因可在靶细胞表达,并能抑制uPA和uPAR的表达.     

Maspin expression in invasive breast cancer: association with other prognostic factors

Maspin is a unique serine protease inhibitor with a molecular weight of 42 kDa. It has been shown to inhibit tumour cell motility and invasion in cell culture, and tumour growth and metastasis in animal models. There is very limited data on the prognostic utility of maspin in human breast cancer. We performed a preliminary study to assess the associations of maspin with other established prognostic factors in invasive breast cancer (IBC). 1068 paraffin-embedded IBCs were immunohistochemically stained with a monoclonal antibody to maspin. A nuclear signal was present in 96% and a cytoplasmic signal in 35% of the cases. Nuclear staining was related to oestrogen (ER) and progesterone receptor (PR) positivity (p < 0.0001), but not to S-phase fraction (SPF) or ploidy. Cytoplasmic staining was related to ER and PR negativity (p < 0.0001), high SPF (p < 0.0001), and aneuploidy (p = 0.003). Thus, maspin nuclear staining was significantly associated with good prognostic factors, while cytoplasmic staining was associated with poor prognostic markers. These findings suggest that the presence of maspin in two different compartments of the cell may have different biological and clinical implications. Additional studies are needed to evaluate further this expression profile of maspin in breast cancer.     

Synergistic antineoplastic action of DNA methylation inhibitor 5-AZA-2'-deoxycytidine and histone deacetylase inhibitor depsipeptide on human breast carcinoma cells

During tumorigenesis, cancer-related genes can be silenced by aberrant DNA methylation and by changes in chromatin structure. It has been reported that 5-aza-2'-deoxycytidine, a potent inhibitor of DNA methylation, in combination with histone deacetylase inhibitors, can produce a synergistic reactivation of these genes. The aim of our study was to investigate the in vitro antineoplastic activity of 5-aza-2'-deoxycytidine in combination with depsipeptide, a potent histone deacetylase inhibitor, against MDA-MB-231 and MDA-MB-435 human breast carcinoma cell lines. We observed that the combination of 5-aza-2'-deoxycytidine and depsipeptide produced a synergistic antineoplastic effect against these tumor cells as compared to either agent administered alone. We also investigated the effect of this drug combination on the activation of maspin and gelsolin expression. These 2 genes whose function is to suppress tumor metastasis have been reported to be silenced by epigenetic events in breast cancer. Using semi-quantitative RT-PCR, we observed that 5-aza-2'-deoxycytidine in combination with depsipeptide produced a greater reactivation of both maspin and gelsolin as compared to each agent alone. The synergistic interaction between 5-aza-2'-deoxycytidine and depsipeptide on breast carcinoma cell lines provides a rationale to investigate this interesting drug combination in future clinical trials on patients with advanced breast cancer.     

Maspin蛋白在宫颈鳞癌中的表达及其与p53蛋白表达的关系

目的研究maspin蛋白在宫颈鳞癌组织中的表达及其与p53蛋白表达的相关性。方法应用免疫组化SP法检测maspin蛋白和p53蛋白在宫颈鳞癌、宫颈上皮内瘤样变、正常宫颈三种组织中的表达。分析maspin蛋白表达与宫颈鳞癌各临床病理参数之间的关系,及宫颈鳞癌组织中maspin与p53蛋白表达的相关性（本研究遵循程序符合本院人体试验委员会制定的伦理学标准,得到该委员会批准）。结果①从正常宫颈上皮组织→宫颈上皮内瘤样变→宫颈鳞癌,maspin蛋白表达逐渐下调,三者比较,差异有显著意义（P〈0．05）。②临床分期越高,分化程度越低的宫颈鳞癌组织中,maspin阳性表达越少。有淋巴结转移的宫颈鳞癌中,maspin阳性率低于无淋巴结转移者,两者比较,差异有显著意义（P〈0．05）。③Maspin与p53蛋白在宫颈鳞癌组织中的表达呈负相关（rs=-0．399,P=0．003）。结论Maspin在宫颈鳞癌的发生、发展过程中起重要的抑制作用,可作为判断宫颈鳞癌患者病情进展、恶性程度及转移潜能的指标之一。Maspin与p53蛋白表达呈负相关,MASPIN可能是P53的效应基因。     

Clinicopathological correlates and prognostic significance of maspin expression in 450 patients after potentially curative resection of node‐positive colonic cancer

Fung C L‐S, Chan C, Jankova L, Dent O F, Robertson G, Molloy M, Bokey L, Chapuis P H, Lin B P C & Clarke S J
(2010) Histopathology 56 , 319–330 Clinicopathological correlates and prognostic significance of maspin expression in 450 patients after potentially curative resection of node‐positive colonic cancer Aims: The tumour suppressor maspin has been investigated for its association with conventional histopathological features in colorectal cancer and for its potential as an independent predictor of survival and response to adjuvant chemotherapy. The aim of this study was to examine associations between maspin expression, other histopathology and survival in a large consecutive series of patients after potentially curative resection of node‐positive colonic adenocarcinoma. Methods and results: Nuclear and cytoplasmic maspin expression in both superficial and deep parts of the tumour were assessed retrospectively by tissue microarray and immunohistochemistry in specimens from 450 patients whose other histopathology had been recorded in a prospective hospital registry of large bowel cancer resections from 1971 to 2001 with a minimum follow‐up of 5 years. Among 13 clinicopathological features examined, the only associations that persisted across all four maspin assessments were stronger expression in right‐ than in left‐sided tumours (P = 0.001–0.011) and stronger expression in high‐grade tumours (P < 0.001–0.007). There was no significant association between intensity of maspin expression and overall survival. Conclusions: In this large and thoroughly documented series of patients with clinicopathological stage C colonic tumour, maspin expression was correlated with few other conventional histopathology variables and was not a significant prognostic factor.     

子宫内膜增生、子宫内膜样腺癌组织中Twist与maspin的表达及相关性分析

目的:研究扭曲蛋白Twist和maspin在典型子宫内膜增生、不典型子宫内膜增生和子宫内膜样腺癌组织中的表达。方法:应用免疫组化检测40例典型子宫内膜增生、40例不典型子宫内膜增生和80例子宫内膜样腺癌组织中Twist、maspin的表达。结果:在典型子宫内膜增生、不典型子宫内膜增生和子宫内膜样腺癌组织中Twist、maspin阳性率分别为10%、37.5%和52.5%,12.5%、42.5%和43.8%。Twist在不典型子宫内膜增生和子宫内膜样腺癌组织中的表达均高于典型子宫内膜增生,差异有统计学意义（P＜0.05）。子宫内膜样腺癌组织中,Twist与组织学分级、浸润深度和淋巴结转移相关,差异有统计学意义（P＜0.05）,maspin与组织学分级、分期和淋巴结转移相关,差异有统计学意义（P＜0.05）。Twist和maspin没有显著相关（r=0.322,P=0.056)。结论:在不典型子宫内膜增生和子宫内膜样腺癌组织中,Twist和maspin蛋白表达不同,表明它们在子宫内膜样腺癌发展中的潜在功能,可能与子宫内膜样腺癌发生有关。     

Cytoplasmic Maspin Expression Correlates with Poor Prognosis of Patients with Adenocarcinoma of the Uterine Cervix

Background

Maspin is known to be a tumor suppressor protein and its prognostic significance in patients with several types of cancer has been reported. To date, however, no study has focused on the association between maspin expression and the prognosis of patients with adenocarcinoma of the uterine cervix. We explored the prognostic value of maspin expression with particular reference to its subcellular localization in patients with adenocarcinoma of the uterine cervix.

Methods

Paraffin-embedded tissue samples from 46 patients diagnosed as adenocarcinoma of the uterine cervix were immunohistochemically analyzed using an antibody for maspin. The patients were followed up for 3 to 165 months (median: 64.2 months) and the prognostic value was evaluated by the log-rank test and the Cox regression hazard model.

Results

A sample was considered maspin-positive if maspin was expressed in only the cytoplasm; 69.6% (32 cases) of the specimens were maspin-positive, and there was significant correlation between positivity and recurrence (P = 0.022). Maspin-positive patients had both shorter disease free survival and shorter overall survival by the log-rank test (P = 0.023, P = 0.043, respectively). By Cox’s multivariate analysis, the International Federation of Obstetrics and Gynecology (FIGO) status was the only independent prognostic factor for disease free survival and overall survival in patients with adenocarcinoma of the uterine cervix.

Conclusion

This is the first report to reveal an association between cytoplasmic maspin expression and the prognosis of patients with adenocarcinoma of the uterine cervix. Although further studies with a larger series of patients and a longer follow up period are necessary, the present results suggest that cytoplasmic maspin expression could be an indicator of unfavorable prognosis in patients with adenocarcinoma of the uterine cervix.