Expression of activated extracellular signal-regulated kinases 1/2 in malignant melanomas: relationship with clinical outcome.
OBJECTIVE
The purpose of the present work was to analyze the protein expression of activated extracellular signal-regulated kinases 1 and 2 (ERK1/2) in a panel of superficial spreading (SSM) and nodular (NM) primary and metastatic melanomas, and to correlate the expression level with clinicopathological parameters.


METHODS
Expression of activated ERK1/2 was examined by immunohistochemistry in 172 primary melanomas (108 SSM and 64 NMs), 67 metastatic lesions, and in 41 benign nevi.


RESULTS
Fifty four percent of primary and 33% of metastatic melanomas expressed variable levels of activated ERK1/2. No immunoreactivity was detected in benign nevi. In 21% of the primaries only cytoplasmic expression was detected, whereas 3% and 30% showed positive immunoreactivity in either nucleus or cytoplasm and nucleus, respectively. Activated ERK1/2 expression varied significantly with the thickness of superficial spreading melanomas, with lower expression in thinner lesions (P = 0.016). A significant correlation between activated ERK1/2 and cyclin D1 (P = 0.031) in nodular, as well as between activated ERK1/2 and cyclin D3 (P = 0.030) in SSMs were observed. The protein level of p27(Kip1) correlated with activated ERK1/2 (P = 0.048) in the nucleus. Furthermore, a strong inverse correlation between activated ERK1/2 and membrane-bound beta-catenin (P = 0.004) in nodular melanomas was revealed. Activation of ERK1/2 did not have any impact on relapse-free or overall survival.


CONCLUSIONS
Our results suggest that activation of ERK1/2 may be involved in cell cycle regulation in SSMs. Moreover, the inverse association between membrane-bound beta-catenin and ERK1/2 in NMs suggest that ERK1/2 activation may play a role in decreasing homotypic interactions through destabilization of beta-catenin.
Jørgensen
Kjersti
K
Department of Pathology, Institute for Cancer Research, The Norwegian Radium Hospital, HF, Montebello, Oslo, Norway.
Holm
Ruth
R
Maelandsmo
Gunhild M
GM
Flørenes
Vivi Ann
VA
D018797:Cell Cycle Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007124:Immunoenzyme Techniques; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology / Q000556:secondary; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000556:secondary; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
C495270:CTNNB1 protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases