TP53 mutations occurred more frequently in differentiated histologic type than in undifferentiated type in the early stage (48.6% vs. 7%, P=0.0006), while the mutations correlated with venous invasion among advanced stage (47.7% vs. 20.7%, P=0.04).
TP53 mutated tumours were poorly differentiated (p<0.001) with a compact pattern (p=0.02), multinucleated (p=0.01) and pleomorphic (p=0.02) cells and frequent vascular invasion (p=0.02).
TP53 is associated with human cancer by mutations that lead to a loss of wild-type p53 function as well as mutations that confer alternate oncogenic functions that enable them to promote invasion, metastasis, proliferation, and cell survival.
TP53 mutations were associated with extramural venous invasion on baseline MRI (78% vs. 65%, p = 0.04), poor pathological tumour regression (23% vs. 36%, p = 0.05) and a trend toward a worse 5-year progression-free survival (PFS; 60% vs. 74%, HR 1.59, p = 0.06).
TP53 gene mutations correlated significantly with advanced surgical stage of disease (P = 0.006) and unfavorable tumor histology types (P = 0.003), whereas the association to myometrial wall invasion did not reach statistical significance (P = 0.054).
A gain-of-function approach was used to observe the effects of lentiviral vector-mediated overexpression of RASSF5 (Lv-RASSF5) on cell growth, invasion and apoptosis, respectively, as indicated by MTT, Transwell and flow cytometry assays, and the expression levels of mammalian sterile 20-like (MST1) kinase, large tumor suppressor 1 (LATS1), proliferating cell nuclear antigen (PCNA), matrix metallopeptidase-9 (MMP-9) and p53 were detected by real-time PCR and western blot assays in OS cells (MG-63 and U-2 OS).
A multivariate Cox analysis revealed that therapy and high p53 expression and venous invasion were independent predictors of unfavorable prognosis in overall survival (<i>p</i>=0.039, <i>p</i>=0.004, and <i>p</i>=0.023, respectively).
A previously described aggregation domain of mutant p53 is not required for p63 or p73 binding; indeed, mutations within this region lead to the acquisition of a mutant p53 phenotype-including a conformational shift, p63/p73 binding and the ability to promote invasion.
A significant association was observed between p53 alterations established either by IHC or direct DNA sequencing and stage (p<0.0001), grade (p<0.001), vascular invasion (p = 0.0005), DNA ploidy (p = 0.0002) and carcinoma in situ (p<0.0001).
A similar frequency of p53 mutations was observed among tumor stages in both intestinal-type and unclassified cancers, but in diffuse tumors mutations tended to be associated with invasion beyond the muscularis propria.
Activating PI-3 kinase and Ras pathway mutations were early events, and inactivating mutations in tumor suppressors including RB1, CDKN2A, and TP53 were associated with invasion in individual cases.
Although p53 activity can impact cell cycle regulation, apoptosis, and DNA repair pathways, the EMT and invasion programs initiated by p53 loss of function or mutation are completely dependent on Snail1 expression.
Although p53 was distributed to the cytoplasm in Apc<sup>Δ716</sup> Trp53<sup>+/R270H</sup> heterozygous tumors, it accumulated in the nuclei at the invasion front, suggesting a regulation mechanism for p53 localization by the microenvironment.
Although mutation of the p53 tumor suppressor gene is one of the most common alterations identified in invasive carcinomas, it is not clear whether mutations usually occur in noninvasive lesions before the development of invasion.
Among the 101 specimens examined, 37(36.6%) showed positivity in staining for p53 protein and 64(63.4%) showed no detectable p53 protein in tumor cells. p53 overexpression was correlated with depth of invasion, lymphatic invasion, lymph node metastasis and distant metastasis.
An active IL-6R/STAT3/miR-34a loop was necessary for EMT, invasion, and metastasis of CRC cell lines and was associated with nodal and distant metastasis in CRC patient samples. p53 activation in CRC cells interfered with IL-6-induced invasion and migration via miR-34a-dependent downregulation of IL6R expression.
An expression of Ki67 in 20% or more of tumor cell nuclei, on the other hand, correlated significantly with histological grade 3 (p < 0.0001), nuclear grade 3 (p < 0.0001), absence of ER (p < 0.0001) and of PR (p < 0.0001), c-erb-B2 expression (p < 0.0001), p53 expression (p < 0.0001) and tumor size (p = 0.0005), but not with nodal invasion.
Any degree of immunohistochemical staining correlated significantly and inversely with c-erb-B2 expression (p = 0.0008), nuclear grade 3 (p = 0.0015), a Ki-67 labeling index > 10% (p = 0.02) and tumor size (p = 0.048), and in a direct fashion with estrogen (p = 0.0003) and progesterone receptor expression (p = 0.0002). mRNA expression of the Bcl-2 gene showed a significant inverse correlation with c-erb-B2 (p = 0.016) and p53 (p = 0.014) expression, as well as with a nuclear grade 3 (p = 0.006), and a direct correlation with estrogen (p = 0.0004) and progesterone (p = 0.001) receptor expression, as well as with nodal invasion (p = 0.04).