Molecular analysis of melanoma precursor lesions.
Atypical (dysplastic) nevi are melanocytic lesions, which are precursors of melanoma as well as markers of increased melanoma risk. Although these lesions exhibit distinct clinical and histological features, their molecular features are largely unknown. To determine whether atypical, compared to benign nevi, from patients with a clinical history of malignant melanoma reveal molecular changes, we analyzed these lesions for the expression of two growth factors (basic fibroblast growth factor and transforming growth factor alpha), their receptors (fibroblast growth factor receptor-1 and epidermal growth factor receptor), and two cell adhesion molecules (MUC18 and alpha v beta 3 integrin), all of which are expressed in primary and metastatic melanomas. The results demonstrated a statistically significant correlation (P = 0.02) between increasing degrees of histological atypia and expression of epidermal growth factor receptor in the epidermal keratinocytes of atypical melanocytic lesions. Furthermore, both atypical and benign nevi revealed considerably high levels of overall gene activity in their dermal melanocytic and epidermal keratinocytic compartments. In contrast, the epidermal-dermal junction wherein melanoma evolves showed little gene activity, suggesting that molecular events occurring adjacent to this junction may be important for melanocytic transformation.
Wang
Y
Y
Department of Medicine, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
Rao
U
U
Mascari
R
R
Richards
T J
TJ
Panson
A J
AJ
Edington
H D
HD
Shipe-Spotloe
J M
JM
Donnelly
S S
SS
Kirkwood
J M
JM
Becker
D
D
D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D051929:CD146 Antigen; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D004416:Dysplastic Nevus Syndrome / Q000378:metabolism / Q000473:pathology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger / Q000032:analysis; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D051929:CD146 Antigen; D015815:Cell Adhesion Molecules; C497902:MCAM protein, human; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D019030:Receptors, Vitronectin; D016211:Transforming Growth Factor alpha; D016222:Fibroblast Growth Factor 2; D066246:ErbB Receptors