Phospho-ERK1/2 levels in XXXX cell nuclei predict responsiveness to radiochemotherapy of @entity420 .

@entity1 @entity41 @entity5 @entity3963 @entity17198 @entity420 @entity55053
UNASSIGNED: Locally advanced @entity420 is treated with radiochemotherapy (RCT) before surgery. The response to RCT is heterogeneous and consensus regarding reliable predictors is lacking. Since the @entity3963 pathway is implicated in radioprotection, we examined pretreatment biopsies from 52 @entity1 by immunohistochemistry for phosphorylated @entity3963 (pERK). Immunostaining for pERK was considerably enhanced by use of alkaline demasking. Nuclear staining occurred in both @entity5 cells and stromal cells. Blind-coded sections were scored by 2 independent investigators. In @entity1 showing no @entity41 after RCT ( @entity17198 ), staining for pERK in @entity5 , but not stromal, cell nuclei was significantly weaker than in @entity1 showing a poor RCT response ( @entity17198 vs @entity55053 : p = 0.0001). Nuclear staining for pERK predicted poor responders, as illustrated by receiver operating characteristic curves with an area under curve of 0.86 (p = 0.0007) and also predicted downstaging (area under curve: 0.76; p = 0.01). A number of controls documented the specificity of the optimized staining method and results were confirmed with another pERK antibody. Thus, staining for pERK in @entity5 cell nuclei can predict the response to RCT and may help spare poor responders this treatment. These results also raise the question whether inhibitors of @entity3963 activation may serve as response modifiers of RCT.
