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Expression of Extracellular Matrix Components Versican, Chondroitin Sulfate, Tenascin, and Hyaluronan, and Their Association with Disease Outcome in Node-Negative Breast Cancer

¹ Dame Roma Mitchell Cancer Research Laboratory, Hanson Institute, Adelaide University, Adelaide, South Australia; ² Department of Anatomy, University of Kuopio, Kuopio, Finland; ³ Department of Oncology, University of Kuopio, Kuopio, Finland; ⁴ Departments of Pathology and Forensic Medicine, University of Kuopio and Kuopio University Hospital, and University of Tampere and Tampere University Hospital, Tampere, Finland; ⁵ Division of Life Sciences, Cell and Molecular Biology, University of Texas at San Antonio, San Antonio, Texas; and ⁶ Department of Anatomical Pathology, Flinders Medical Centre, Adelaide, South Australia

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.

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