Whole-mount analysis has begun to address the histologic significance of the focal evolution of TP53 mutation in a pre-existing cancer and to reveal its role throughout the process of tumor progression.
In addition, recent studies have also shown that gain-of-function (GOF) mutant p53 proteins drive metabolic reprogramming in cancer cells, contributing to cancer progression.
Our data showed that (1) the frequency of C609T NQO1 was significantly increased in TNM stage III HCC patients; (2) no significant association was found between p53 expression and C609T polymorphism of NQO1 gene; and (3) a tumor/non-tumor (T/N) ratio > 1.27 of NQO1 expression revealed by real-time qPCR analyses was positively correlated with poorer survival in patients with tumors >5 cm, suggesting that an increase of NQO1 expression may be an indicator of advanced tumor progression.
To better isolate the potential effects of p53 gene mutations per se on tumor progression, we chose to examine patients with advanced disease in whom surgery was not performed (stages IIIA, IIIB, and IV).
The genetic findings of this patient suggest that the increased genetic instability could contribute to tumor progression as well as to treatment resistance, possibly in the background of the clonal deletion of TP53.
Cox-Regression analysis showed a significant and independent influence of TP53 mutation on tumour progression in comparison with tumour grade, stage and history of prior bladder cancer.
Altogether, N-ras p21 alterations are registered at earlier stages than p53 alterations in melanoma development and may be of aetiological importance, whereas p53 alterations may be associated with tumour progression in the late stages.(ABSTRACT TRUNCATED AT 250 WORDS)
Notably, TP53 mutation, which has been used as a marker of tumor progression in many human cancers, was less significant in associating with progression in this study (P = 0.04) than was p16 or pRb alteration (P = 0.001).
It has been well established that in addition to abrogating the tumor-suppressive function of wild-type p53, mutant p53 gains new functions and actively contributes to various stages of tumor progression.
On the contrary, intratumor heterogeneity of p53 mutations indicates that the type of the p53 mutations may also be relevant for selection and expansion of new subclones leading to tumor progression.
Based on our data, the p53 mutation appears to be an uncommon (2%) genetic event in PXA formation and does not appear to be involved in tumor progression.
Tumor suppressor p53 is frequently deleted or mutated in aggressive and high-grade ovarian cancer, probably aggravating cancer progression and increasing mortality.
In conclusion, although DAP kinase alteration was relatively rare, DAP kinase alteration and/or p53 mutation may associate with tumor progression in soft-tissue LMSs.
Gliomas with a high grade of malignancy, negative immunoexpression of alpha-internexin, or positive immunoexpression for p53 were more likely to be associated with tumor progression during pregnancy.
These data suggest that, in endometrial carcinomas, Bcl-2 and p53 alterations may play important roles in determining whether tumor progression from early to advanced stages will occur.
Thus, altered p53 pathways, such as p53 gene mutation and mdm2-mediated inactivation of p53, may play a pathogenetic role in this form of tumor progression showing myxoid MFH-like morphology in liposarcoma, as has been suggested in dedifferentiated liposarcoma.