In addition, pERK immunoreactivity was predomi nantly nuclear whereas cytoplasmic positivity was located within a subset of tumors, This staining pattern is in line with former investigations in colon likewise as other neoplasms, namely, endometrial, head and neck tumors and melanomas, In addition, complete nuclear or cytoplasmic ERK staining was independent of nuclear or cytoplasmic pERK status, in our cohort.
This observation is in agreement with former scientific studies in non small cell lung and endometrial cancer too as in melanomas and could been explained through the hypothesis that pERK immunopositivity could arise as a consequence of ERK hyperactivation rather than overexpression, In addition we display that in the know high nuclear, but not cyto plasmic, ERK immunopositivity is correlated with tumor stage, Interestingly, our results show that nuclear pERK expression parallels tumor grade and tumor stage in keeping with findings of prior research in NSCLC and prostate cancer, This observation is in contrast with a past investigation through which pERK expression was not correlated with tumor stage, whereas there are actually other scientific studies in many other tumors that have failed to sub stantiate a constructive correlation involving pERK expression and classical clinicopathological parameters, Taking into account that in our examine standard colorectal mucosa displays minimum nuclear pERK expression, our success talk in favor with the possible part of this molecule in tumor evolution too as, in the acquisition of the additional aggressive pheno kind in colorectal carcinogenesis. Along this line, it’s been advised that constitutively active ERKs are cap able of affecting gene expression, having the ability to influence lots of in the hallmarks of carcinogenesis, It could possibly be hypothesised that as colorectal cancer progresses to a extra advanced condition, a rise within the activation of your MAP kinase signal transduction pathway happens, Sad to say, the statistical power with the existing investigation is diminished due to the compact cohort of pERK good scenarios.
Further studies of larger cohorts are warranted to confirm our effects. Along this line, pERK expression has been shown to be related with bad prognosis in colorectal carcinomas, It’s been speculated that the activation in the MAPK path way initiates cellular processes, which could result OSI-420 in either favorable or worse clinical end result, a reality because of the complex signal transduction network ERKs are concerned in. In actual fact, adverse results can be observed, based on the intensity and duration of your promito genic signal, The aforementioned findings are quite considerable in see of your fact that protein kinases signify a group of molecular targets characterized by a cancer specific probable, permitting the growth of new generation chemotherapeutic agents acting as kinase inhibitors.