Clinical significance of the expression of c-Ski and SnoN, possible mediators in TGF-beta resistance, in primary cutaneous melanoma.
BACKGROUND
Loss of TGF-beta growth control is considered as a hallmark of several human neoplasms including melanoma. Resistance of cancer cells to TGF-beta has been linked to mutations in proteins involved in the TGF-beta pathway. In melanoma such mutations have not been observed. C-Ski and SnoN, two structurally and functionally highly homologous proteins, are known as negative regulators in the TGF-beta signaling pathway. C-Ski and SnoN expression levels and subcellular localization have been associated with clinicopathological parameters and tumour progression in several human malignancies. In melanoma cell lines, high c-Ski and SnoN expression levels have been described.


OBJECTIVE
The objective of this study was to evaluate the clinical value of c-Ski and SnoN expression in primary cutaneous melanoma.


METHODS
We evaluated c-Ski and SnoN expression by immunohistochemical staining in 120 primary melanomas. Possible associations between c-Ski and SnoN staining patterns and clinicopathological parameters were analyzed.


RESULTS
Nuclear c-Ski expression was significantly associated with thicker and ulcerated tumours. The percentage of SnoN positivity was higher in ulcerated tumours and in the sentinel node positive group.


CONCLUSIONS
These results suggest that c-Ski and SnoN, mediators in TGF-beta resistance, might be implicated in melanoma growth and progression.
Boone
Barbara
B
Department of Dermatology, Ghent University Hospital, Ghent, Belgium. barbara.boone@ugent.be
Haspeslagh
Marc
M
Brochez
Lieve
L
D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D015398:Signal Transduction / Q000502:physiology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; C060615:SKIL protein, human; D016212:Transforming Growth Factor beta; C060614:SKI protein, human