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Reduced Expression of the Small Leucine-rich Proteoglycans, Lumican, and Decorin Is Associated with Poor Outcome in Node-negative Invasive Breast Cancer¹

Departments of Pathology [S. T., P. H. W.], Biochemistry and Molecular Biology [L. C. M.], Community Health Sciences [E. V. K.], and Preventive Oncology and Epidemiology, CancerCare Manitoba [C. N., E. V. K., M. P.], Epidemiology Unit Manitoba Health [E. V. K.], University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, R3E OW3 Canada; Departments of Anatomy, University of British Columbia [C. R.], and Medicine [S. C.], Johns Hopkins University School of Medicine, Baltimore, Maryland; Genetics Unit, Shriners Hospital for Children, Montreal, Quebec, H3G 1A6 Canada [P. J. R.]

Purpose: To examine the prognostic significance of lumican and decorin, two abundant small leucine-rich proteoglycans in breast tissue stroma.

Experimental design: Lumican and decorin expression was examined in a cohort of 140 invasive breast carcinomas by Western blot analysis. All cases were axillary lymph node-negative and treated by adjuvant endocrine therapy.

Results: Lumican and decorin expression was highly correlated (r = 0.45, P < 0.0001), but although low levels of lumican were associated with large tumor size (P = 0.0496), negative estrogen receptor (P = 0.0024) and progesterone receptor status (P = 0.0116), and increased host inflammatory response (P = 0.0077), low decorin levels were associated only with large tumor size (P = 0.0496). However, using univariate analysis, low levels of lumican and decorin were both associated with a shorter time to progression (P = 0.0013 and 0.0262) and poorer survival (P = 0.001 and 0.0076). In multivariate analysis using the Cox regression model, low decorin was also shown to be an independent predictive factor for recurrence (hazard ratio 2.25: 95% confidence interval 1–5, P = 0.047) and survival (hazard ratio 3.39: 95% confidence interval 1.2–9.6, P = 0.021).

Conclusions: These results suggest that low levels of small leucine-rich proteoglycans in breast tumors may be associated with a worse prognosis in lymph node-negative invasive breast carcinomas and warrant further study with larger patient cohorts.

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