Expression and prognostic relevance of activated extracellular-regulated kinases (ERK1/2) in breast cancer

Extracellular-regulated kinases (ERK1, ERK2) are members of the MAPK signaling pathway, which are phosphorylated in response to extracellular stimuli and translocate to the nucleus where they can activate nuclear transcription factors. Although they have been extensively studied in vitro, little is known about their role in the behavior of tumor cells in vivo. In our present study, 148 clinical breast cancer samples (120 cases with follow-up) were studied for expression of ERK1 and ERK2 and their phosphorylated forms (p-ERK1, p-ERK2) by immunoblotting, and p-ERK1/2 expression in the corresponding paraffin sections was analyzed by immunohistochemistry (IHC). The results were correlated with clinical and histological prognostic parameters, follow-up data, and expression of 7 cell-cycle regulatory proteins which had been analyzed before. High p-ERK1 expression as determined by immunoblots correlated significantly with a low rate of recurrences or fatal outcome (p=0.007 and 0.008) and was an independent indicator of long relapse-free and overall survival in multivariate analysis. By IHC, strong p-ERK staining was associated with early stages (p=0.020), negative nodal status (p=0.003) and long recurrence-free survival (p=0.017). In contrast, expression of the unphosphorylated kinases was not associated with clinical and histological parameters except a positive correlation with estrogen receptor status. Comparison with the expression of cell-cycle proteins corroborates our conclusion that activation of ERK1 and ERK2 is not associated with enhanced proliferation of mammary carcinomas, but might be a new predictor of a favourable prognosis.

Eingereicht von: Karin Milde-Langosch

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