title: Increased expression of stem cell markers in malignant melanoma.
abstract: The potential role of stem cells in neoplasia is a subject of recent interest. Three markers of melanocytic stem cells have been described recently. CD166 is expressed on the surface of mesenchymal stem cells and has been found on human melanoma cell lines. CD133 is expressed on the surface of dermal-derived stem cells that are capable of differentiating into neural cells. Nestin is an intermediate filament expressed in the cytoplasm of neuroepithelial stem cells. In this study, we evaluate the expression of these markers and possible differences among banal nevi, primary melanoma, and metastastic melanoma. Tissue microarrays containing normal tissue and 226 melanocytic lesions (71 banal nevi, 71 in situ and invasive melanomas, and 84 metastatic melanomas) were studied by immunohistochemistry using monoclonal antibodies CD166, CD133, and nestin. A significantly greater percentage of melanomas (combined primary and metastatic) contained cells that expressed CD166 (P=0.005), CD133 (P=0.003), and nestin (P=0.03) than banal nevi. Only nestin showed a statistical difference when comparing primary and metastatic melanoma (P=0.05). A stepwise increase in the proportion of lesions expressing all three markers was observed from banal nevi (2/19) to primary melanomas (8/17) to metastatic melanoma (19/28), P=0.0005. All cases of metastatic melanoma expressed at least one stem cell marker. The increased expression of CD166, CD133, and nestin in melanoma suggests that progression to malignant melanoma likely involves genetic pathways instrumental to stem cell biology and normal tissue development. Further studies and characterization of these pathways may also reveal new prognostic markers for a disease whose prognosis in advanced stages is dismal.
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Walter M
authors.initials: WM
authors.lastname: Klein
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Wu
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Andres J P
authors.initials: AJ
authors.lastname: Klein-Szanto
authors.forename: Steven R
authors.initials: SR
authors.lastname: Tahan
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D005326:Fetal Proteins / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000032:analysis; D008544:Melanocytes / Q000737:chemistry / Q000473:pathology*; D008545:Melanoma / Q000737:chemistry / Q000473:pathology*; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000032:analysis; D064231:Nestin; D009506:Nevus / Q000145:classification / Q000473:pathology*; D010455:Peptides / Q000032:analysis; D011379:Prognosis; D012878:Skin Neoplasms / Q000737:chemistry / Q000473:pathology*; D046888:Tissue Array Analysis; D015854:Up-Regulation; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; D006023:Glycoproteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D010455:Peptides; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C577484:NES protein, human; C000606023:PROM1 protein, human