Distribution and colocalization of markers for proliferation, invasion, motility and neoangiogenesis in benign melanocytic naevi and malignant melanomas.
BACKGROUND
Melanomas are heterogeneous tumours, and differentiation from other melanocytic lesions may cause problems. It may be possible that the distribution and/or colocalization pattern of different markers in the lesions can enable a more accurate diagnosis of melanocytic tumours.


OBJECTIVE
To test this hypothesis, melanocytic naevi, primary melanomas and metastases were investigated.


METHODS
The distribution and colocalization of markers for proliferation, invasion, angiogenesis and motility of the tumour cells were investigated using antibodies directed against actin, cathepsin B (CatB), transforming growth factor-beta, vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen/Ki-67 and basic fibroblast growth factor (FGF-2). In addition, melanoma markers (HMB-45 and Melan-A) and proteins unrelated to melanoma progression [epidermal growth factor (EGF) and cathepsin H] were investigated.


RESULTS
Malignant melanomas tended to express more markers of malignancy compared with melanocytic naevi, and the differences were statistically significant for EGF and actin immunoreactivity: melanocytic naevi displayed clear EGF labelling more often (60% vs. 5%) and melanomas showed more intense actin labelling (70% vs. 0%). HMB-45+ cells to a large extent also stained with antibodies to CatB but not to EGF or actin; EGF-, FGF-2- and VEGF-immunoreactive cells were predominantly HMB-45-. Similar combinations were observed in melanocytic naevi and in melanomas.


CONCLUSIONS
Labelling with EGF may improve the differential diagnosis of melanocytic neoplasias. However, we did not detect a clear-cut increase of markers of malignancy in melanoma. Cells expressing multiple malignancy markers were also found in some melanocytic naevi; this may confirm the dormant potential of melanocytic naevi for melanoma development.
Fröhlich
E
E
Anatomisches Institut, Osterbergstrasse 3, 72074 Tübingen, Germany. froehlich@anatu.uni-tuebingen.de
Mack
A F
AF
Garbe
C
C
Klessen
C
C
D014408:Biomarkers, Tumor / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D003937:Diagnosis, Differential; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000098:blood supply / Q000175:diagnosis* / Q000556:secondary; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009508:Nevus, Pigmented / Q000098:blood supply / Q000175:diagnosis* / Q000473:pathology; D012878:Skin Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000473:pathology
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D004815:Epidermal Growth Factor