title: Evaluation of the expression of stem cell markers in human breast cancer reveals a correlation with clinical progression and metastatic disease in ductal carcinoma.
abstract: The tumor stem cell theory could explain how patients with metastatic disease show clinical relapse several months after starting treatment due to the survival of a small group of cells with unique characteristics. We examined the distribution and expression of a panel of stem cell markers in human breast cancer primary tumors. Human breast tissues were processed for immunohistochemistry, and RNA was extracted for analysis by quantitative-PCR. Immunohistochemical assay revealed that CD44 was strongly expressed in background endothelia and epithelia. CD133 expression was lost in tumor-associated endothelial cells. Conversely, CD49b was strongly stained in the tumors, associated vessels and ducts but was weakly stained in the background epithelia. q-PCR analysis revealed that CD44 and PSCA were reduced in patients with poor outcome (metastatic disease and death from breast cancer), with a marked reduction in ductal carcinoma, particularly with metastasis to bone although these did not reach significant difference. CD133 was significantly reduced in patients with metastatic disease and was also significantly reduced in patients with ductal carcinoma/bone metastasis. Conversely, CD49F was increased in patients with a poor outcome and those with ductal cancer and bone metastases. This is the first study to determine the distribution and expression pattern of these stem cell markers in human breast cancer. There was a significant association between loss of expression and metastatic disease in patients with breast cancer. Such differential expression may play a part in breast cancer disease progression, and suggests that the current stem cell theory may not hold true for all cancer types.
authors.affiliation: Metastasis and Angiogenesis Research Group, Institute of Cancer and Genetics, Cardiff School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: Tracey Amanda
authors.initials: TA
authors.lastname: Martin
authors.forename: Wen Guo
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000096:biosynthesis; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary*; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000473:pathology* / Q000628:therapy; D018450:Disease Progression; D005260:Female; D058851:GPI-Linked Proteins / Q000096:biosynthesis; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007150:Immunohistochemistry; D039421:Integrin alpha2 / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010455:Peptides; D011960:Receptors, Estrogen / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D039421:Integrin alpha2; D009363:Neoplasm Proteins; C000606023:PROM1 protein, human; C110843:PSCA protein, human; D010455:Peptides; D011960:Receptors, Estrogen