ORIGINAL ARTICLE

Activation of the extracellular signal regulated kinase (ERK) pathway in human melanoma

L Zhuang¹, C S Lee¹, R A Scolyer¹, S W McCarthy¹, A A Palmer¹, X D Zhang³, J F Thompson², L P Bron² and P Hersey³

¹ Department of Anatomic Pathology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
² Sydney Melanoma Unit and the Melanoma and Skin Cancer Research Institute, Royal Prince Alfred Hospital
³ Oncology and Immunology Unit, Newcastle Mater Misericordiae Hospital, Newcastle, NSW 2300, Australia

Correspondence to:
Correspondence to:
Professor P Hersey
Oncology and Immunology Unit, Room 443, David Maddison Clinical Sciences Building, Newcastle Mater Misericordiae Hospital, Cnr King and Watt Streets, Newcastle, NSW 2300, Australia; Peter.Hersey{at}newcastle.edu.au

Background: Several studies suggest that melanoma may be resistant to treatment because of resistance to apoptosis and that this may be the result of activation of the extracellular signal regulated kinase (ERK1/2) pathway.

Aims: To test this hypothesis by examining the expression of ERK1/2 and its activated form in histological sections of melanoma and its relation to known prognostic features of the disease.

Materials/Methods: Immunohistochemistry with antibodies to ERK1/2 and phosphorylated ERK (p-ERK) was performed on formalin fixed sections from 42 primary melanomas, 38 metastases, and 20 naevi. Fourteen of the primary melanomas were in the radial and 28 in the vertical growth phase.

Results: ERK1/2 was widely expressed (100%) in all the (pigmented) lesions studied. p-ERK1/2 expression was much lower in compound (32.4%) and dysplastic (54.5%) naevi than in primary melanoma (nodular 78.8%, superficial spreading 67%) and subcutaneous metastases (76.3%). p-ERK expression was much lower in lymph node metastases (48.5%), suggesting that the microenvironment may influence the activation of ERK. There was a (non-significant) trend for p-ERK expression to be higher in thick (>1.0 mm) versus thin (1.0 mm) melanoma (p = 0.23). There was a trend for overall survival to be related to p-ERK expression in patients with melanoma over 1 mm in thickness.

Conclusions: Expression of activated ERK1/2 in melanocytic lesions appears to be related to malignant potential so that activation of ERK1/2 may be important in melanoma progression. These results provide important histological support for the proposal that inhibition of this signalling pathway may be useful in treatment of melanoma.

Abbreviations: DFS, disease free survival; ERK, extracellular signal regulated kinase; IRS, immunoreactive score; MAPK, mitogen activated protein kinase; OS, overall survival; p-ERK, activated extracellular signal regulated kinase

Keywords: extracellular signal regulated kinase 1/2; melanoma; pathogenesis; activated extracellular signal regulated kinase 1/2; signalling pathway

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