EGFR, p16, HPV Titer, Bcl-xL and p53, Sex, and Smoking As Indicators of Response to Therapy and Survival in Oropharyngeal Cancerстатья из журнала
Аннотация: Purpose To prospectively identify markers of response to therapy and outcome in an organ-sparing trial for advanced oropharyngeal cancer. Patients and Methods Pretreatment biopsies were examined for expression of epidermal growth factor receptor (EGFR), p16, Bcl-xL, and p53 as well as for p53 mutation. These markers were assessed for association with high-risk human papillomavirus (HPV), response to therapy, and survival. Patient variables included smoking history, sex, age, primary site, tumor stage, and nodal status. Results EGFR expression was inversely associated with response to induction chemotherapy (IC) (P = .01), chemotherapy/radiotherapy (CRT; P = .055), overall survival (OS; P = .001), and disease-specific survival (DSS; P = .002) and was directly associated with current smoking (P = .04), female sex (P = .053), and lower HPV titer (P = .03). HPV titer was significantly associated with p16 expression (P < .0001); p16 was significantly associated with response to IC (P = .008), CRT (P = .009), OS (P = .001), and DSS (P = .003). As combined markers, lower HPV titer and high EGFR expression were associated with worse OS (ρ EGFR = 0.008; ρ HPV = 0.03) and DSS (ρ EGFR = 0.01; ρ HPV = 0.016). In 36 of 42 biopsies, p53 was wild-type, and only one HPV-positive tumor had mutant p53. The combination of low p53 and high Bcl-xL expression was associated with poor OS (P = .005) and DSS (P = .002). Conclusion Low EGFR and high p16 (or higher HPV titer) expression are markers of good response to organ-sparing therapy and outcome, whereas high EGFR expression, combined low p53/high Bcl-xL expression, female sex, and smoking are associated with a poor outcome. Smoking cessation and strategies to target EGFR and Bcl-xL are important adjuncts to the treatment of oropharyngeal cancer.
Год издания: 2008
Авторы: Bhavna Kumar, Kitrina G. Cordell, Julia S. Lee, Francis P. Worden, Mark E. Prince, Huong H. Tran, Gregory T. Wolf, Susan G. Urba, Douglas B. Chepeha, Theodoros N. Teknos, Avraham Eisbruch, Christina Tsien, Jeremy M. G. Taylor, Nisha J. D’Silva, Kun Yang, David M. Kurnit, Joshua A. Bauer, Carol R. Bradford, Thomas E. Carey
Издательство: Lippincott Williams & Wilkins
Источник: Journal of Clinical Oncology
Ключевые слова: Head and Neck Cancer Studies, Lung Cancer Treatments and Mutations, Cancer-related Molecular Pathways
Другие ссылки: Journal of Clinical Oncology (PDF)
Journal of Clinical Oncology (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)
Journal of Clinical Oncology (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)
Открытый доступ: bronze
Том: 26
Выпуск: 19
Страницы: 3128–3137