Figure 8.

Activation of the MEK-ERK pathway in cutaneous lesions of patients under vemurafenib treatment. Components and targets of the pathway are detected by immunofluorescence microscopy in normal skin (first column) compared with perilesional skin (second column), early invasive SCCs (third column), and well-differentiated SCCs (fourth column). (A) Under vemurafenib, pERK (red) is upregulated in the nuclei of basal epidermal cells; KRT2 (green) demarcates terminally differentiated upper epidermal cells. (B) The intensity of MMP1 staining (red) significantly increases under vemurafenib treatment and shows enrichment in the invading epithelia. (C) MMP3 displays a moderate epithelial staining (red) in normal skin that gains intensity under treatment and progression towards SCC. Also dermal cells stain positive for MMP3. No signs of myofibroblast differentiation; αSMA (green) staining is restricted to vascular structures. (D) Decreased intensity of TIMP-1 (red) correlates with an acquired invasive phenotype under vemurafenib; CD3ζ-positive T-cells (green) do not show any significant accumulation. (E) Faint epithelial GM-CSF signals (red) are accompanied by a well-detectable staining of stromal cells under vemurafenib, particularly in SCCs. The epidermal basal layer is defined by staining for KRT15 (green). Scale bar = 150 µm.