p53 Gene Status as a Predictor of Tumor Response to Induction Chemotherapy of Patients With Locoregionally Advanced Squamous Cell Carcinomas of the Head and Neck

Temam, Stéphane; Flahault, Antoine; Périé, Sophie; Monceaux, Guy; Coulet, Florence; Callard, P; Bernaudin, Jean-François; Guily, Jean Lacau St; Fouret, Pierre

doi:10.1200/jco.2000.18.2.385

Cited by 134 publications

(92 citation statements)

References 42 publications

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“…This association between p53 and HPV status also was seen in our study but it was not statistically significant. This may be due to mutant p53 that is resistant to E6 degradation in some HPV-HR tumors (37,39). Although immunohistochemistry would also detect wild-type p53, overexpression of wild-type p53 in HNC is unlikely.…”

Section: Discussionmentioning

confidence: 99%

Association between p53 and Human Papillomavirus in Head and Neck Cancer Survival

Smith

Wang

Rubenstein

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: High-risk human papillomavirus (HPV-HR) is a significant risk factor for head and neck cancer (HNC), abrogating normal p53 function. In addition, HPV and p53 have been associated with prognosis of these tumors but the findings have been inconsistent. We examined p53 expression and HPV-HR individually and jointly for differences in predicting HNC survival. Methods: HNC patients (n = 294) were evaluated for p53 by immunohistochemical staining. HPV was detected by PCR/dot blot hybridization and sequencing. Results: HNC tumors showed 48% with p53 overexpression and 27% with HPV-HR. Multivariate analyses showed that p53 positivity was significantly associated with higher risk of disease-specific [hazard ratio (HR); 2.0; 95% confidence interval (95% CI), 1.1-3.7] and recurrence-free mortality (HR, 2.8; 95% CI, 1.4-5.3). HPVÀ cases had significantly worse disease-specific

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Section: Discussionmentioning

confidence: 99%

Association between p53 and Human Papillomavirus in Head and Neck Cancer Survival

Smith

Wang

Rubenstein

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…[160][161][162][163][164][165][166][167][168] Here, we will only briefly report on the putative role of p53 with respect to 5-FU efficacy, as this relationship has been most extensively studied. Mutations in the p53 gene and p53 overexpression have been associated with 5-FU chemoresistance both in vitro [169][170][171] and in vivo in colorectal, 124,[172][173][174][175] head and neck, 176,177 and breast cancer. 178 However, results in some other studies are less unequivocal.…”

Section: Jg Maring Et Almentioning

confidence: 99%

Genetic factors influencing Pyrimidine-antagonist chemotherapy

et al. 2005

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Pyrimidine antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of these pyrimidine prodrugs into active compounds. Interindividual variation in the activity of metabolising enzymes can affect the extent of prodrug activation and, as a result, act on the efficacy of chemotherapy treatment. Genetic factors at least partly explain interindividual variation in antitumour efficacy and toxicity of pyrimidine antagonists. In this review, proteins relevant for the efficacy and toxicity of pyrimidine antagonists will be summarised. In addition, the role of germline polymorphisms, tumourspecific somatic mutations and protein expression levels in the metabolic pathways and clinical pharmacology of these drugs are described. Germline polymorphisms of uridine monophosphate kinase (UMPK), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and methylene tetrahydrofolate reductase (MTHFR) and gene expression levels of OPRT, UMPK, TS, DPD, uridine phosphorylase, uridine kinase, thymidine phosphorylase, thymidine kinase, deoxyuridine triphosphate nucleotide hydrolase are discussed in relation to 5-FU efficacy. Cytidine deaminase (CDD) and 5 0 -nucleotidase (5NT) gene polymorphisms and CDD, 5NT, deoxycytidine kinase and MRP5 gene expression levels and their potential relation to dFdC and ara-C cytotoxicity are reviewed.

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“…Recent studies have described many biological markers correlating with outcome. 13,[15][16][17][18][19][20][21][22][23][24][25][26][27] However, only a few have been tested for predictive accuracy after chemoradiation treatment. Such markers include those associated with cell cycle control (cyclin D1, retinoblastoma gene product (RB), P16, P21 and P27), apoptosis (TP53, MDM2, TP73 and BCL-2), growth regulation (EGFR), cyclooxygenase-2 (COX-2 and ki-67), focal adhesion signaling (cortactin), hypoxia (CA9, HIF-1a) and sensitivity to chemotherapy (XPA, MRP2 and MDR1).…”

mentioning

confidence: 99%

Molecular markers predict outcome in squamous cell carcinoma of the head and neck after concomitant cisplatin‐based chemoradiation

Broek

Wildeman

Rasch

et al. 2009

Intl Journal of Cancer

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Not all patients with squamous cell carcinomas of the head and neck (HNSCC) benefit from concurrent cisplatin-based chemoradiation, but reliable predictive markers for outcome after chemoradiation are scarce. We have investigated potential prognostic biomarkers for outcome in a large group of patients. Ninety-one tumor biopsies taken from consecutive HNSCC patients were evaluated for protein expression on a tissue microarray. Using immunohistochemistry, 18 biomarkers, involved in various cellular pathways were investigated. Univariable and multivariable proportional hazard analyses were performed to investigate associations between each individual marker and outcome. In addition, the global test was used to test all variables simultaneously and selected combinations of markers for an overall association with local control. Univariable analysis showed statistically significant increased relative risks of RB, P16 and MRP2 for local control and MDR1 and HIF-1a for overall survival. MRP2, MDR1 and P16 levels were positively associated with outcome whereas RB and HIF-1a had a negative relationship. Using Goeman's global testing no combination of markers was identified that was associated with local control. Grouping the markers according to their function revealed an association between a combination of 3 markers (P16, P21 and P27) and outcome (p 5 0.05) was found. In the multivariable analysis, MRP2 and RB remained significant independent predictive markers for local control. This study describes the prognostic value of biomarkers for the outcome in patients uniformly treated with concurrent chemoradiation. MRP2 and RB were found to be associated with outcome in patients treated with concurrent chemoradiation. ' 2009 Wiley-Liss, Inc.

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p53 Gene Status as a Predictor of Tumor Response to Induction Chemotherapy of Patients With Locoregionally Advanced Squamous Cell Carcinomas of the Head and Neck

Abstract: p53 gene mutations are strongly associated with a poor risk of both objective and major responses to chemotherapy. Contact mutations are associated with the lowest risk of major response to chemotherapy.

Cited by 134 publications

References 42 publications

Association between p53 and Human Papillomavirus in Head and Neck Cancer Survival

Association between p53 and Human Papillomavirus in Head and Neck Cancer Survival

Genetic factors influencing Pyrimidine-antagonist chemotherapy

Molecular markers predict outcome in squamous cell carcinoma of the head and neck after concomitant cisplatin‐based chemoradiation

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