title: p53 and P-glycoprotein expression are significant prognostic markers in advanced head and neck cancer treated with chemo/radiotherapy.
abstract: The development of biological markers of response to chemo- and radiotherapy to judge benefit to risk ratios for toxic treatments is still at an experimental stage. Tumour cell death is largely by apoptosis and the p53 gene has a major influence on this. P-glycoprotein (P-gp) accumulation has been correlated with treatment failure in several types of cancer. p53 and P-gp expression were studied in 111 advanced head and neck cancers treated with radiotherapy and up to four courses of synchronous or sequential chemotherapy. The probability of survival at 5 years for patients in the trial as a whole was 27.7%, while the cohort used for this marker project was 29.4%. Among the subjects used for the marker study at the time of analysis, 13 remained disease-free and 18 were alive. Immunohistochemistry was used to assess p53 and P-gp expression; 27/111 (24%) head and neck cancers demonstrated p53/P-gp expression and 33/111 (30%) were both p53- and P-gp- negative. In univariate analysis, both p53 and P-gp expression were associated with reduced disease-free and overall survival. Multivariate analysis revealed tumour size, p53, and P-gp expression as the most powerful pretreatment prognosticators in the study cohort. Long-term follow-up results suggest that p53 and P-gp co-expression predicts the biological behaviour or the outcome following chemo/radiotherapy in advanced head and neck cancer.
authors.affiliation: Department of Oral Medicine and Pathology, WHO Collaborating Centre for Oral Cancer and Precancer, The Guys, King's and St Thomas' Schools of Medicine and Dentistry of King's College London, Caldecot Road, London SE5 9RW, UK.
authors.forename: S
authors.initials: S
authors.lastname: Warnakulasuriya
authors.forename: C
authors.initials: C
authors.lastname: Jia
authors.forename: N
authors.initials: N
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Houghton
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53