Clinical significance of the expression of c-Ski and SnoN, possible mediators in TGF-beta resistance, in primary cutaneous melanoma

Abstract

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.

Conclusion: These results suggest that c-Ski and SnoN, mediators in TGF-beta resistance, might be implicated in melanoma growth and progression.