Publication: Expression of Skp2 and p27KIP1 in naevi and malignant melanoma of the skin and its relation to clinical outcome
Authors
Woenckhaus, C. ; Maile, S. ; Uffmann, S. ; Bansemir, M. ; Dittberner, T. ; Poetsch, M. ; Giebel, J.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Skp2 (S-phase kinase associated protein 2)
controls progression from G- to S-phase by promoting
the proteolysis of the cyclin dependent kinase inhibitor
p27KIP1. Despite the fact that a p27KIP1 decrease has
been documented in melanoma progression, the role of
Skp2 in these tumours is unknown. We therefore
examined by immunohistochemistry the expression of
Skp2, p27KIP1 and Ki-67 in 10 naevi (Ns), 15
superficial spreading melanomas (SSMs), 10 nodular
melanomas (NMs) and 14 melanoma metastases (Ms).
Nuclear Skp2 expression augmented with increasing
malignancy (Ns: 1.4%, SSMs: 5.6%, NMs: 17.3%, Ms:
19.1%). In all tumours nuclear Skp2 expression
correlated with Ki-67 (p=0.024) and inversely with
p27KIP1 (p=0.007). A cytoplasmic reaction for Skp2
was also observed in most tumours and its expression
decreased from Ns (12.3%) to SSMs (7.9%) and NMs
(4.5%). In contrast, Ms showed an increase of
cytoplasmic Skp2 (11.9%) that correlated with its
nuclear expression (p=0.016). While nuclear Skp2
expression correlated with the pT-level (p=0.023), Clarklevel
(p=0.023) and Breslow index (p=0.019), the
cytoplasmic Skp2 expression might be of biological
significance only in NMs since it correlated with tumour
depth (p=0.02) and pT-level (p=0.025). Our data
suggests that Skp2 could contribute to melanoma progression. This is further highlighted by the fact that
vertical growth phase (VGP) melanomas show
significant higher nuclear Skp2 expressions when
compared with the harmless radial growth phase (RGP)
(p=0.047). Also nuclear Skp2 expression correlates with
a reduced survival time (p=0.025) in melanoma.
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