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血小板反应蛋白-1在尿路上皮癌中的表达:预后意义及其与p53改变、肿瘤血管生成和细胞外基质成分的关系

Thrombospondin-1 expression in urothelial carcinoma: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components.

作者信息

Ioachim E, Michael M C, Salmas M, Damala K, Tsanou E, Michael M M, Malamou-Mitsi V, Stavropoulos N E

机构信息

Department of Pathology, University Hospital of Ioannina, Ioannina, Greece.

出版信息

BMC Cancer. 2006 May 29;6:140. doi: 10.1186/1471-2407-6-140.

DOI:10.1186/1471-2407-6-140
PMID:16732887
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1538616/
Abstract

BACKGROUND

Thrombospondin-1 (TSP-1) is an extracellular matrix component glycoprotein, which is known to be a potent inhibitor of angiogenesis and may be important in cancer invasiveness. We examined the TSP-1 expression in correlation with conventional clinicopathological parameters to clarify its prognostic significance in bladder cancer. In addition, the possible correlation of TSP-1 expression with microvessel count, VEGF expression, p53 expression as well as with the expression of the extracellular matrix components was studied to explore its implication in vascularization and tumour stroma remodeling.

METHODS

The immunohistochemical expression of TSP-1 in tumour cells and in the tumour stroma was studied in 148 formalin-fixed paraffin-embedded urothelial cell carcinoma tissue samples.

RESULTS

TSP-1 was detected in perivascular tissue, at the epithelial-stromal junction, in the stroma and in tumour cells in the majority of the cases. In tumour cells, low TSP-1 expression was observed in 43% of the cases, moderate and high in 7%, while 50% showed absence of TSP expression. A higher TSP-1 immunoreactivity in well and moderately differentiated tumours compared to poorly differentiated was noted. PT1 tumours showed decreased TSP-1 expression in comparison to pTa and pT2-4 tumours. Increased tumour cell TSP-1 expression was related to increased microvessel density. In the tumour stroma, 37% of the cases showed small amount of TSP-1 expression, 7.5% moderate and high, while 55% of the cases showed absence of TSP-1 stromal immunoreactivity. Stromal TSP-1 expression was inversely correlated with tumour stage and tumour size. This expression was also positively correlated with microvessel density, VEGF expression and extracellular matrix components tenascin and fibronectin. Using univariate and multivariate analysis we didn't find any significant correlation of TSP-1 expression in superficial tumours in both tumour cells and tumour stroma in terns of the risk of recurrence and disease progression

CONCLUSION

Our data suggest that both tumour and stromal TSP-1 expression may play a role in tumour aggressiveness and angiogenesis. In addition, the correlation of stromal TSP-1 expression with extracellular matrix components fibronectin and tenascin indicate its possible implication in tumour stroma remodeling.

摘要

背景

血小板反应蛋白-1(TSP-1)是一种细胞外基质成分糖蛋白,已知它是血管生成的强效抑制剂,可能在癌症侵袭中起重要作用。我们研究了TSP-1表达与传统临床病理参数的相关性,以阐明其在膀胱癌中的预后意义。此外,还研究了TSP-1表达与微血管计数、VEGF表达、p53表达以及细胞外基质成分表达之间的可能相关性,以探讨其在血管生成和肿瘤基质重塑中的意义。

方法

对148例福尔马林固定石蜡包埋的尿路上皮细胞癌组织样本中肿瘤细胞和肿瘤基质中TSP-1的免疫组化表达进行了研究。

结果

在大多数病例中,在血管周围组织、上皮-基质交界处、基质和肿瘤细胞中均检测到TSP-1。在肿瘤细胞中,43%的病例观察到低TSP-1表达,7%为中度和高度表达,而50%的病例显示无TSP表达。与低分化肿瘤相比,高分化和中分化肿瘤中TSP-1免疫反应性更高。与pTa和pT2-4肿瘤相比,PT1肿瘤显示TSP-1表达降低。肿瘤细胞TSP-1表达增加与微血管密度增加有关。在肿瘤基质中,37%的病例显示少量TSP-1表达,7.5%为中度和高度表达,而55%的病例显示无TSP-1基质免疫反应性。基质TSP-1表达与肿瘤分期和肿瘤大小呈负相关。这种表达也与微血管密度、VEGF表达以及细胞外基质成分腱生蛋白和纤连蛋白呈正相关。使用单变量和多变量分析,我们未发现浅表肿瘤中肿瘤细胞和肿瘤基质中TSP-1表达与复发风险和疾病进展之间存在任何显著相关性。

结论

我们的数据表明,肿瘤和基质TSP-1表达可能在肿瘤侵袭性和血管生成中起作用。此外,基质TSP-1表达与细胞外基质成分纤连蛋白和腱生蛋白的相关性表明其可能参与肿瘤基质重塑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05fa/1538616/1210f036ec3b/1471-2407-6-140-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05fa/1538616/1210f036ec3b/1471-2407-6-140-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05fa/1538616/1210f036ec3b/1471-2407-6-140-1.jpg

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