Elevated osteopontin and thrombospondin expression identifies malignant human breast carcinoma but is not indicative of metastatic status.
BACKGROUND
Our previous characterization of a human breast tumor metastasis model identified several candidate metastasis genes. The expression of osteopontin (OPN) correlated with the metastatic phenotype, whereas thrombospondin-1 (TSP-1) and tyrosinase-related protein-1 (TYRP-1) correlated with the nonmetastatic phenotype of independent MDA-MB-435 cell lines implanted orthotopically into athymic mice. The aim of the present study was to examine the cellular distribution of these molecules in human breast tissue and to determine whether the relative expression level of these three genes is associated with human breast tumor metastasis.


METHODS
Sixty-eight fresh, frozen specimens including 31 primary infiltrating ductal carcinomas, 22 nodal metastases, 10 fibroadenomas, and five normal breast tissues were evaluated for OPN expression, TSP-1 expression and TYRP-1 expression. Immunohistochemistry was performed to monitor the cellular distribution and to qualitatively assess expression. Quantitative analysis was achieved by enrichment of breast epithelial cells using laser-capture microdissection and subsequent real-time, quantitative PCR.


RESULTS
The epithelial components of the breast tissue were the source of OPN and TSP-1 expression, whereas TYRP-1 was present in both the epithelial and stromal components. Both OPN and TSP-1 expression were significantly higher in malignant epithelial sources over normal and benign epithelial sources, but no difference in expression levels was evident between primary tumors with or without metastases, nor between primary and metastatic carcinomas.


CONCLUSIONS
Elevated expression of OPN and TSP-1 may play a role in the pathogenesis of breast cancer. The multiplex analysis of these molecules may enhance our ability to diagnose and/or prognosticate human breast malignancy.
Wang-Rodriguez
Jessica
J
Department of Pathology, University of California, San Diego, La Jolla, USA. jwrodriguez@ucsd.edu
Urquidi
Virginia
V
Rivard
Amber
A
Goodison
Steve
S
D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000175:diagnosis* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000175:diagnosis / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008562:Membrane Glycoproteins; D014442:Monophenol Monooxygenase / Q000235:genetics; D053495:Osteopontin; D010088:Oxidoreductases; D016133:Polymerase Chain Reaction / Q000379:methods; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis; D012795:Sialoglycoproteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D019700:Thrombospondin 1 / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D011506:Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D019700:Thrombospondin 1; D053495:Osteopontin; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase