Inhibition of TP53 and activation of MYC signaling pathways in normal astrocytes exposed to GBM-EVs may be a mechanism by which GBM manipulates astrocytes to acquire a phenotype that promotes tumor progression.
Wild-type p53 repressed gene expression of the basic FGF and its mutant activated it in vitro, implying one of the possible pathways in tumor progression.
The biopsy specimens should be evaluated for p53 overexpression, because our data indicate that persistent p53 overexpression in uroepithelial lesions after BCG treatment is an ominous finding for probable tumor progression.
Moreover, significantly increased expression of p53 in advanced-stage cervical carcinoma implies that inactivation of p53 is associated with tumor progression.
The present study examines the role of HPV infection in relation to p53 and the extent of the tumor proliferative compartment reflected by cyclin D1 and Ki-67 expression during various phases of tumor progression in the oral epithelium.
These data indicate that p53 inactivation and/or Ras activation might play a role in acute transformation of BCR/ABL- CMPD and that the molecular mechanisms of tumor progression may be different in BCR/ABL+ versus BCR/ABL-CMPD.
Collectively, these data show that ROCK2 activation induces malignancy in ras<sup>Ha</sup>-initiated/promoted papillomas in the context of p53 loss and novel NF-κB expression, whereas increased tissue rigidity and cell motility/contractility help mediate tumour progression.
Additional follow-up and further studies are required to better define the role of p53 nuclear overexpression and 17p deletions as markers of tumor progression in human bladder cancer.
Tumor progression in renal cell carcinoma (RCC) can be explained by a multistep model, in which the activation of certain oncogenes such as c-neu and c-fos appear to be early events in tumorigenesis, while the expression of p53 and pan-ras are found in advanced stages.
Low-grade lymphoma of small lymphocytic type disclosed p53+ large cells (paraimmunoblasts) that may play a role in tumor progression in this lymphoma subtype. p53 was also strongly expressed in the nuclei of Reed Sternberg cells from 19 of 37 cases of Hodgkin's disease, including six cases of mixed cellularity, and 13 cases of nodular sclerosing type.
Not surprisingly, many of the altered proteins have previously been implicated in the regulation of tumor progression (e.g., p53 tumor suppressor protein and c-myc oncogene protein among many others).
We demonstrated p53 protein expression in 33% of naevi (17 out of 51), 35% of primary melanomas (20 out of 58), and 70% of metastatic lesions (15 out of 21). p53 expression in benign lesions was weaker than in malignant lesions in intensity and percentage of cells staining. p53 protein expression in melanomas increased in intensity and percentage of cells staining with tumour progression.
We searched for studies that: (1) used immunohistochemistry to assess p53 expression in esophageal biopsies of BE patients and (2) reported subsequent neoplastic progression.
Further studies are warranted to determine whether the association between p53 overexpression and advanced stage disease is due to accumulation of genetic lesions during tumor progression or whether p53 alterations confer a more virulent phenotype.
TP53 and MDM2 genes and their protein expression were evaluated in frozen and paraffin-embedded tissue from 27 patients with malignant fibrous histiocytoma to elucidate the relationship between them, their implication in tumor progression mechanisms and their possible diagnostic-prognostic value in malignant fibrous histiocytoma.
Our data provide no evidence for a causal relationship between the loss of p53 activity and increased VEGF expression that is observed during tumor progression.
These results demonstrate for the first time that Survivin variants are differentially expressed in breast cancer according to tumour progression and treatment and suggest that Survivin-3B might act as an antiapoptotic factor in this lesion, with its expression regulated by p53.
MYCN amplification and p53 inactivation are two typical characteristics of aggressive neuroblastomas and are strongly associated with cancer progression and treatment failure.
Detection of p53 nuclear overexpression in 20% or more tumor cells was the only independent marker of tumor progression in univariate and multivariate analyses (p = 0.004, adjusted relative risk 8.6, 95% confidence interval 2 to 40).