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细胞外基质成分多功能蛋白聚糖、硫酸软骨素、腱生蛋白和透明质酸的表达及其与淋巴结阴性乳腺癌疾病转归的关联

Expression of extracellular matrix components versican, chondroitin sulfate, tenascin, and hyaluronan, and their association with disease outcome in node-negative breast cancer.

作者信息

Suwiwat Supaporn, Ricciardelli Carmela, Tammi Raija, Tammi Markku, Auvinen Paivi, Kosma Veli-Matti, LeBaron Richard G, Raymond Wendy A, Tilley Wayne D, Horsfall David J

机构信息

Dame Roma Mitchell Cancer Research Laboratory, Hanson Institute, Adelaide University, Adelaide, South Australia.

出版信息

Clin Cancer Res. 2004 Apr 1;10(7):2491-8. doi: 10.1158/1078-0432.ccr-03-0146.

Abstract

PURPOSE

The purpose is to determine whether the levels of expression of extracellular matrix components in peritumoral stroma are predictive of disease outcome for women with node-negative breast cancer.

EXPERIMENTAL DESIGN

Tumor tissue from 86 patients with node-negative breast cancer was examined by immunohistochemical staining for the expression of versican, chondroitin sulfate (CS), tenascin, and hyaluronan (HA). With the exception of HA, the expression of the extracellular matrix components was measured by video image analysis. Statistical correlation of the immunohistochemical data with clinicopathological characteristics and disease outcome was performed.

RESULTS

All of the extracellular matrix components were present in the peritumoral stroma of the entire study cohort. In contrast, immunoreactivity within the cancer cell was observed in 82% of tumors for HA, 12% for CS, and 4% for tenascin; no immunostaining of cancer cells for versican was observed for any of the tumors. Cox regression and Kaplan-Meier analyses indicated that elevated expression of stromal versican predicted increased risk and rate of relapse in this cohort. Elevated expression of tenascin was predictive of increased risk and rate of death only. Although neither CS nor HA were predictive of disease outcome in this cohort, tumor size was predictive of increased risk and rate of both relapse and survival.

CONCLUSIONS

Elevated expression within peritumoral stromal matrix of versican and tenascin was predictive of relapse-free and overall survival, respectively, in women with node-negative breast cancer.

摘要

目的

确定肿瘤周围基质中细胞外基质成分的表达水平是否可预测淋巴结阴性乳腺癌女性的疾病预后。

实验设计

对86例淋巴结阴性乳腺癌患者的肿瘤组织进行免疫组织化学染色,检测多功能蛋白聚糖、硫酸软骨素(CS)、腱生蛋白和透明质酸(HA)的表达。除HA外,通过视频图像分析测量细胞外基质成分的表达。对免疫组织化学数据与临床病理特征及疾病预后进行统计相关性分析。

结果

所有细胞外基质成分均存在于整个研究队列的肿瘤周围基质中。相比之下,82%的肿瘤中观察到癌细胞内HA呈免疫反应性,12%的肿瘤中CS呈免疫反应性,4%的肿瘤中腱生蛋白呈免疫反应性;所有肿瘤的癌细胞中均未观察到多功能蛋白聚糖的免疫染色。Cox回归和Kaplan-Meier分析表明,基质多功能蛋白聚糖表达升高预示该队列中复发风险和复发率增加。腱生蛋白表达升高仅预示死亡风险和死亡率增加。虽然CS和HA在该队列中均不能预测疾病预后,但肿瘤大小可预测复发和生存的风险及发生率增加。

结论

在淋巴结阴性乳腺癌女性中,肿瘤周围基质中多功能蛋白聚糖和腱生蛋白的表达升高分别预示无复发生存和总生存。

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