Reduced expression of the small leucine-rich proteoglycans, lumican, and decorin is associated with poor outcome in node-negative invasive breast cancer.
OBJECTIVE
To examine the prognostic significance of lumican and decorin, two abundant small leucine-rich proteoglycans in breast tissue stroma.


METHODS
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.
Troup
Sandra
S
Department of Pathology, University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, R3E OW3 Canada.
Njue
Catherine
C
Kliewer
Erich V
EV
Parisien
Michelle
M
Roskelley
Cal
C
Chakravarti
Shukti
S
Roughley
Peter J
PJ
Murphy
Leigh C
LC
Watson
Peter H
PH
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis*; D058575:Decorin; D018450:Disease Progression; D018572:Disease-Free Survival; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007632:Keratan Sulfate / Q000096:biosynthesis*; D007930:Leucine / Q000737:chemistry; D000071234:Lumican; D008198:Lymph Nodes / Q000378:metabolism; D011379:Prognosis; D011509:Proteoglycans / Q000096:biosynthesis*; D013997:Time Factors; D016896:Treatment Outcome
D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; C000604306:LUM protein, human; D000071234:Lumican; D011509:Proteoglycans; D007632:Keratan Sulfate; D007930:Leucine