The predictive value of p53 and p33(ING1b) in patients with Dukes'C colorectal cancer
ABSTRACT Identification of biological markers that may predict response to chemotherapy would allow the individualization of treatment by enabling selection of patients most likely to benefit from chemotherapy. The aims of this study were to determine whether p53 mutation status and p53 and p33(ING1b) protein expression can predict which patients with Dukes' C colorectal cancer following curative surgical resection respond to adjuvant chemotherapy with 5-fluorouracil (5-FU).
Patients with Dukes'C colorectal cancer (n = 41) were studied. DNA was extracted and analysed for p53 mutation using PCR-based direct DNA sequencing. Tumours were analysed for p53 protein expression by immunohistochemistry using DO-7 monoclonal antibody and for p33(ING1b) protein expression using GN1 monoclonal antibody.
There was a significant association between p53 mutation status analysed by gene sequencing and overall and metastasis-free survival (P = 0.03 and 0.004, respectively, log-rank test). By contrast, no significant correlation was found between p53 and p33(ING1b) protein expression and overall or metastasis-free survival.
In patients with Dukes'C colorectal cancer who underwent curative surgical resection of the primary tumour, followed by 5-FU-based adjuvant chemotherapy, p53 mutation status as assessed by gene sequencing is a significant predictor of overall and metastasis-free survival.
[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND: Cell killing by ionizing radiation is triggered by DNA-damage involving the p53 gene as major player in cell death induction. p53 is frequently inactivated in cancer which prevents apoptosis after extensive DNA-damage. METHOD: We summarize considerations to conduct a predictive marker trial mandatory before clinical application of p53 for individualized therapy. RESULTS: PART 1 is an academic driven prospective randomized trial addressing individualized, marker adapted radiation therapy for the first time. Patients suffering from T2/T3 rectal cancer appropriate for preoperative radiation will be included. The design qualifies the trial to determine the relevance of p53 gene mutation as a marker guiding the choice of therapy. A delay of surgery after radiation is implemented to improve detection of the radiation effect on the tumor. CONCLUSIONS: This predictive marker trial intends to provide the level of evidence I that the p53 genotype and time of surgery are prognostic markers. Furthermore should the predictive value of p53 genotype be evaluated as marker to select patients for preoperative radiation therapy.European Surgery 04/2010; 42(1):18-23. DOI:10.1007/s10353-010-0514-5 · 0.26 Impact Factor
Head and Neck Cancer, 03/2012; , ISBN: 978-953-51-0236-6
[Show abstract] [Hide abstract]
ABSTRACT: ING genes (ING1-5) were identified has tumor suppressor genes. ING proteins are characterised as Type II TSGs since they are involved in the control of cell proliferation, apoptosis and senescence. They may also function as Type I TSGs since they are also involved in DNA replication and repair. Most studies have reported that they are frequently lost in human tumors and epigenetic mechanisms or misregulation of their transcription may be involved. Recently, studies have described that this loss may be caused by micro-RNA inhibition. Here, we summarize the current knowledge on ING functions, their involvement in tumor suppression and, in order to give a full assessment of the current knowledge, we review all the studies that have examined ING status in human cancers.Cancer letters 12/2013; 345(1). DOI:10.1016/j.canlet.2013.11.016 · 5.02 Impact Factor