title: Bcl-2 expression predicts radiotherapy failure in laryngeal cancer.
abstract: Early stage laryngeal cancer can be effectively cured by radiotherapy or conservative laryngeal surgery. In the UK, radiotherapy is the preferred first line treatment. However, up to 25% of patients with T2 tumours will demonstrate locally persistent or recurrent disease at the original site, requiring salvage surgery to achieve a definitive cure. Patients experiencing treatment failure have a relatively poor prognosis. A retrospective analysis was conducted consisting of 124 patients with early stage (T1-T2, N0) laryngeal squamous cell carcinoma. In total, 62 patients who failed radiotherapy were matched for T stage, laryngeal subsite and smoking history to a group of 62 patients successfully cured by radiotherapy. Using immunohistochemistry the groups were compared for expression of apoptotic proteins: bcl-2, bcl-X(L), bax, bak and survivin. Radioresistant laryngeal cancer was associated with bcl-2 (P < 0.001) and bcl-X(L) (P = 0.005) expression and loss of bax expression (P = 0.012) in pretreatment biopsies. Bcl-2 has an accuracy of 71% in predicting radiotherapy outcome. The association between expression of bcl-2, bcl-X(L) and bax with radioresistant cancer suggests a potential mechanism by which cancer cells avoid the destructive effects of radiotherapy. Predicting radioresistance, using bcl-2, would allow the clinician to recommend conservative laryngeal surgery as an alternative first line treatment to radiotherapy.
authors.affiliation: Postgraduate Medical Institute, University of Hull, Hull York Medical School, Hull, UK.
authors.forename: P
authors.initials: P
authors.lastname: Nix
authors.forename: L
authors.initials: L
authors.lastname: Cawkwell
authors.forename: H
authors.initials: H
authors.lastname: Patmore
authors.forename: J
authors.initials: J
authors.lastname: Greenman
authors.forename: N
authors.initials: N
authors.lastname: Stafford
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D019254:Genes, bcl-2 / Q000502:physiology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000532:radiotherapy* / Q000601:surgery; D007825:Laryngectomy; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011237:Predictive Value of Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D011836:Radiation Tolerance / Q000502:physiology*; D012189:Retrospective Studies; D000077022:Survivin; D017211:Treatment Failure
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin